Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Recurrence

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Antirheumatic Agents

Micronutrients

Hematinics

Vitamins

Amino Acids

Dexamethasone

Gemcitabine

Azacitidine

Decitabine

Rituximab

Melphalan

Vitamin B 6

Pyridoxal

Pyridoxine

Dexamethasone acetate

BB 1101

Busulfan

Vorinostat

Antineoplastic Agents, Immunological

Immunologic Factors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antimetabolites

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Histone Deacetylase Inhibitors

Folic Acid

Vitamin B Complex

Trace Elements

Vitamin B6

Glutamine

Folate

Vitamin B9

Busulfan test dose 32 mg/m2 by vein either as outpatient before Day -12 or as inpatient on Day -11. Busulfan pharmacokinetics performed with test dose and first dose on Day -8. Doses on Days -6 and -5 adjusted to target an AUC of 4,000 microMol.min-1. Dexamethasone 8 mg by vein twice a day from Day -11 AM to Day -2 PM. Caphosol oral rinses 30 mL four times a day used from Day -9. Oral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9. Pyridoxine 100 mg by vein or mouth three times a day from Day -1. Vorinostat 1000 mg by vein on Day -11 through Day -2. Gemcitabine loading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8. Melphalan 60 mg/m2 by vein on Days -3 and -2. Azacitidine starting dose 15 mg/ m2 by vein on Day -11. Stem cell transplant on Day 0. Patients with CD20+ tumors receive rituximab 375 mg/m2 by vein on Days -9.

Starting dose 15 mg/ m2 by vein on Day -11.

1000 mg by vein on Day -11 through Day -2.

Loading dose 75 mg/m2 by vein followed by 22775 mg/m2 by vein on Day -8.

Busulfan test dose 32 mg/m2 by vein either as outpatient before Day -12 or as inpatient on Day -11. Busulfan pharmacokinetics performed with test dose and first dose on Day -8. Doses on Days -6 and -5 adjusted to target an AUC of 4,000 microMol.min-1.

8 mg by vein twice a day from Day -11 AM to Day -2 PM.

Caphosol oral rinses 30 mL four times a day used from Day -9.

Caphosol

Oral glutamine, 15 g four times a day, swished, gargled and swallowed from Day -9.

100 mg by vein or mouth three times a day from Day -1.

Yago Nieto, MD, PHD

The goal of this clinical research study is to find the highest tolerable dose of azacitidine that can be given with vorinostat, gemcitabine, busulfan, and melphalan, with a stem cell transplant, and with or without rituximab. Researchers also want to learn about the safety and level of effectiveness of this combination.

Study Groups:

If you have been found to be eligible to take part in this study and you agree, you will be assigned to a dose level of azacitidine based on when you join this study. Up to 7 dose levels of azacitidine will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of azacitidine is found.

All participants will receive the same dose level of vorinostat, gemcitabine, busulfan, and melphalan, and all patients with B-cell cancer will receive the same dose of rituximab. However, if the first group has bad side effects, the dose level of gemcitabine may be lowered for all other groups.

Busulfan Test Dose:

You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in your blood levels changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches your body size. You will most likely receive this as an outpatient during the week before you are admitted to the hospital. If it cannot be given as an outpatient, you will be admitted to the hospital on Day -12 (12 days before your stem cells are returned to your body) and the test dose will be given on Day -11.

About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points and will help the study doctor determine what your dose of busulfan should be on study. These blood samples will be drawn at various timepoints before you receive busulfan and over about the next 11 hours. The blood samples will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose of busulfan.

On Days -14, -13, and -12, you will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

Study Drug Administration (for all patients):

In stem cell transplants, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive your stem cells are called plus days.

Beginning on Day -9, you will swish the liquids caphosol and glutamine in your mouth 4 times a day, for about 2 minutes each time. You will swish these liquids every day until you leave the hospital. You will swallow the glutamine. These drugs are used to help decrease the risk of side effects in the mouth and throat.

On Day -11 through Day -2, you will take vorinostat by mouth, with food. One hour later each day, you will receive azacitidine by vein over 1 hour. You will receive dexamethasone by vein 2 times each day.

If you have a B-cell cancer, you will receive rituximab (a treatment used for certain lymphomas) by vein over 3-6 hours as part of standard of care, on Day -9.

On Day -8, you will receive gemcitabine by vein over 4 ½ hours.

On Days -8, -7, -6, and -5, you will receive busulfan by vein over 2 hours.

On Day -3, you will receive gemcitabine by vein over 4 ½ hours and then melphalan by vein over 30 minutes.

On Day -2, you will receive melphalan by vein over 30 minutes.

On Day -1, you will rest (you will not receive chemotherapy).

On Day 0, you will receive your stem cells by vein over about 30-60 minutes.

You will receive 3 more doses of palifermin by vein over 15-30 seconds on Days 0, +1, and +2.

As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin 1 time each day starting on Day +5 until your blood cell levels return to normal.

Study Tests:

About 100 days after the transplant:

* You will have a physical exam.
* Blood (about 4 teaspoons) and urine will be collected for routine tests.
* If the doctor thinks it is needed, you may have a bone marrow aspiration and biopsy to check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

Length of Study:

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are released from the hospital, you will continue as an outpatient in the Houston area to be monitored for infections and transplant-related complications.

You will be taken off study about 100 days after the transplant. You may be taken off study early if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

This is an investigational study. Azacitidine, vorinostat, gemcitabine, busulfan, melphalan, and rituximab are all FDA approved and commercially available. The use of these study drugs in combination is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma

Azacitidine/Vorinostat/GemBuMel With Autologous Stem-Cell Transplant (SCT) in Patients With Refractory Lymphomas

Maximum tolerated dose (MTD) of azacitidine based on DLT was defined as any Grade 4 nonhematologic and noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 3 days at peak severity. For dose finding, the continunal reassessment method was used with a target DLT probability per cohort of 25%. Azacitidine doses were chosen adaptively for sucessive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 3.

EFS is defined as the time from transplantation to either relapse, second tumors, or death, whichever occurred first, or last contact. EFS was analzyed by the individual disease groups rather than the cohort dose levels.

M.D. Anderson Cancer Center

Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

Azacitidine Dose Level 1

Azacitidine 25 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

Azacitidine Dose Level 2

Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

Azacitidine Dose Level 3

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Disease-DLBCL

Disease-Hodgkin lymphoma

Disease-T-cell lymphoma

Disease-Other B-cell lymphoma

Overall Study Group

Nieto, Yago / Stem Cell Transplantation and Cellular Therapy

Frequency of DLT

DLBCL patients who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

DLBCL

Hodgkin Lymphoma patients who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

Hodgkin Lymphoma

T-cell NHL patients who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

T-cell NHL

Other B-cell lymphoma (Follicular lymphoma and Mantle cell lymphoma) who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto SCT

Other B-cell Lymphoma

Participants With Event-free Survival (EFS)

Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)

Azacitidine 25mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)

Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)

Overall Study

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Busulfan test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5. Palifermin 60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2. SAHA 1,000 mg by mouth on Days -8 to -3. Gemcitabine loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3. Carfilzomib 27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1. SAHA 1,000 mg by mouth on Days -7 to -3. Melphalan 60 mg/m2 by vein on Days -3 and -2. Stem cell transplant on Day 0. Dexamethasone 8 mg by vein twice a day from Day -9 PM to Day -2 PM. Caphosol oral rinses 30 mL four times a day from Day -9 until discharge. Oral glutamine 15 g four times a day, swished, gargled and spit on Day -9 until discharge. Pyridoxine 100 mg by vein or mouth three times a day from Day -1.

27 mg/m2 by vein on Days -7 and -6, then on Days -2 and -1

Carfilzomib

SAHA

Loading dose of 75 mg/m2 followed by continuous infusion of the remaining dose of 1875 mg/m2 by vein on Days -8 and -3.

Test dose of 32 mg/m2 by vein on Day -10 if inpatient, on Day -12 if outpatient, then AUC of 4,000 microMol.min on Days -8 to -5.

Stem Cell Transplant (SCT)

60 microgram/kg by vein on Days -12 to -10 and Days 0, +1 and +2.

Palifermin

8 mg by vein twice a day from Day -9 PM to Day -2 PM.

30 mL oral rinse four times a day from Day -9 until discharge.

15 g four times a day, swished, gargled and spit on Day -9 until discharge.

Yago Nieto, MD,PHD

The goal of this clinical research study is to learn if carfilzomib and vorinostat combined with gemcitabine, busulfan, and melphalan with a stem cell transplant will help to control multiple myeloma (MM). Researchers also want to learn about the safety and effectiveness of this combination.

Busulfan Test Dose:

Participant will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in participant's blood changes over time. This information will be used to decide the next dose needed to reach the target blood level that matches participant's body size. Participant will most likely receive this as an outpatient during the week before they are admitted to the hospital. If it cannot be given to participant as an outpatient, they will be admitted to the hospital on Day -11 (11 days before participant's stem cells are returned to their body) and the test dose will be given on Day -10.

About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points and will help the study doctor decide what participant's dose of busulfan in this study should be. These blood samples will be drawn at various timepoints before participant receives busulfan and over about the next 11 hours. The blood samples will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in participant's vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, participant will receive the standard fixed dose of busulfan.

If participant receives the busulfan test dose as an outpatient:

On Days -12, -11, and -10, participant will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

Participant will be admitted to the hospital on Day -9.

If participant receives the busulfan test dose as an inpatient:

On Days -14, -13, and -12, participant will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

Participant will be admitted to the hospital on Day -11.

Study Drug Administration (for all participants):

With stem cell transplants, the days before participant receives their stem cells are called minus days. The day participant receives the stem cells is called Day 0. The days after participant receives their stem cells are called plus days.

Beginning on Day -9, participant will swish the liquids caphosol and glutamine in their mouth 4 times a day, for about 2 minutes each time. Participant will swish these liquids every day until they leave the hospital. These drugs are used to help decrease the risk of side effects in the mouth and throat.

On Day -9 through Day -2, participant will receive dexamethasone 2 times a day by vein over about 10 minutes.

On Day -8 through Day -2, participant will take vorinostat by mouth, with food.

On Day -8, participant will receive gemcitabine by vein over about 4 hours.

On Days -8, -7, -6, and -5, participant will receive busulfan by vein over about 3 hours.

On Days -7 and -6, participant will receive carfilzomib by vein over about 2-10 minutes.

On Day -3, participant will receive gemcitabine by vein over about 4 hours and melphalan by vein over 30 minutes.

On Day -2, participant will receive carfilzomib by vein over about 2-10 minutes and melphalan by vein over about 30 minutes.

On Day -1, participant will receive carfilzomib by vein over about 2-10 minutes.

On Day 0, participant will receive their stem cells by vein over about 30-60 minutes.

Participant will receive 3 more doses of palifermin by vein over about 15-30 seconds on Days 0, +1 and +2.

As part of standard care, participant will receive G-CSF (filgrastim) as an injection just under their skin 1 time a day starting on Day +5 until their blood cell levels return to normal.

Study Tests:

About 1 month, 100 days, 6 months, 1 year, and then about every 3-6 months for at least 2 years after the transplant:

* Participant will have a physical exam.
* Blood (about 4 tablespoons) will be drawn for routine tests, to learn how the transplant has taken, and to check the status of the disease.

About 100 days after the transplant, participant will have a bone marrow biopsy and aspiration to check the status of the disease. To collect a bone marrow biopsy and aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone and bone marrow is withdrawn through a large needle. This will be repeated once a year or earlier, if participant's doctor thinks it is needed.

Once a year, participant will have x-rays of all the bones in their body to check the status of the disease.

The study staff will also stay in contact with participant's local doctor to find out if the disease comes back and to check how they are doing.

Length of Treatment:

As part of standard care, participant will remain in the hospital for about 3-4 weeks after the transplant. After participant is released from the hospital, they will continue as an outpatient in the Houston area to be monitored for infections and transplant-related complications.

Participant will be taken off study about 2 years after the transplant. Participant may be taken off study early if the disease gets worse, if intolerable side effects occur, or if they are unable to follow study directions.

If for any reason participant wants to leave the study early, they must talk to the study doctor. It may be life-threatening to leave the study after participant has started to receive the study drugs but before they receive the stem cell transplant because their blood cell counts will be dangerously low.

This is an investigational study. Carfilzomib and melphalan are FDA approved for the treatment of MM. Vorinostat is FDA approved for the treatment of cutaneous lymphoma. Busulfan is FDA approved for the treatment of leukemia. Gemcitabine is FDA approved for the treatment of lymphoma, breast cancer, and lung cancer. The use of these study drugs in combination is investigational. The study doctor can explain how the study drugs are designed to work.

Up to 75 participants will take part in this study. All will be enrolled at MD Anderson.

Carfilzomib/SAHA Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant in Myeloma

Carfilzomib/SAHA Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant for Patients With Refractory/Relapsed Myeloma

Complete remission (CR) rate defined as percentage of number of complete responses in total number of patients treated.

Response rates (CR; CR/VGPR; RR) reported along with corresponding 95% confidence intervals. Logistic regression used to model the association between response rates and prognostic factors. Overall survival (OS) and progression free survival (PFS) estimated by the Kaplan-Meier method. Comparison of time to event endpoints by subgroups made using the log-rank test. Cox proportional hazards regression employed for univariate and multivariate analysis on time-to-event outcomes.

Belinostat

Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an area under curve (AUC) of 4,000 microMol.min-1.

Caphosol oral rinses 30 mL four times a day used from Day -8. Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8.

Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1. Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2. Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2. Participants with cluster of differentiation antigen 20 (CD20+) tumors receive Rituximab 375 mg/m2 by vein on Day -9.

Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3.

Melphalan 60 mg/m2/d by vein on Day -2. Stem cell transplant by vein given on Day 0.

Busulfan "test dose" administered by vein on Day -10. Test dose of 32 mg/m2 based on actual body weight. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -8. Doses on Days -6 and -5 subsequently adjusted to target an AUC of 4,000 microMol.min-1.

Caphosol oral rinses 30 mL four times a day used from Day -8.

Oral Glutamine, 15 g swished, gargled and swallowed four times a day starting on Day -8.

Pyridoxine 100 mg by vein or mouth three times a day staring on Day -1

Starting dose of Belinostat 100 mg/ m2/day by vein on Day -9 through Day -2.

Azacitidine 15 mg/m2/day by vein on Day -9 through Day -2.

Gemcitabine 75 mg/m2 by vein administered as a loading dose followed by prolonged infusion on Days -8 and -3.

Melphalan 60 mg/m2 by vein on Days -3 and -2.

Stem Cell Transplant

The goal of this clinical research study is to find the highest tolerable dose of belinostat that can be given in combination with azacitidine, gemcitabine, busulfan, and melphalan to patients who are scheduled to have a stem cell transplant. If you have diffuse large B-cell lymphoma (DLBCL), you will also receive rituximab. Researchers also want to learn about the safety and effectiveness of this combination.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose level of belinostat based on when you join this study. Up to 5 dose levels of belinostat will be tested. At least 2 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of belinostat is found.

All participants will receive the same dose level of azacitidine, gemcitabine, busulfan, melphalan. All patients with DLBCL will also receive the same dose of rituximab. However, if the first group has intolerable side effects, the dose level of gemcitabine may be lowered for all other groups.

Busulfan Test Dose:

In stem cell transplants, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive your stem cells are called plus days.

You will receive a test dose of busulfan by vein over about 60 minutes. This low-level test dose of busulfan is to check how the level of busulfan in your blood level changes over time. This information will be used to decide the next dose needed to reach the dose level that matches your body size. You will most likely receive this as an outpatient during the week before you are admitted to the hospital. If busulfan cannot be given to you as an outpatient, you will be admitted to the hospital on Day -11 (11 days before your stem cells are returned to your body) and the test dose will be given on Day -10.

On either Day -11 or -10, blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing 11 times over the 11 hours after your test dose of busulfan. PK testing measures the amount of study drug in the body at different time points and will help the study doctor determine what your dose of busulfan should be on study. The PK blood draws will be repeated again on the first day of high-dose busulfan treatment (Day -8). A temporary heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose of busulfan.

About 2 or 3 days before receiving the test dose of busulfan (depending on if you are an inpatient or outpatient), you will receive palifermin by vein over about 30 seconds each day to help decrease the risk of side effects in the mouth and throat.

Study Drug Administration (all patients):

Beginning on Day -8, you will swish caphosol and glutamine in your mouth 4 times a day for about 2 minutes each time. You will swish these liquids every day until you leave the hospital. You will swallow the glutamine. These drugs are used to help decrease the risk of side effects in the mouth and throat.

On Day -9 through Day -2, you will receive belinostat continuously by vein. You will also receive azacitidine by vein on each of these days over about 30 minutes. Depending on the type of cancer you have, you will also receive rituximab by vein over 3-6 hours as part of standard care on Day -9. The study staff will tell you if you will receive rituximab.

On Day -8, you will receive gemcitabine by vein over 4½ hours.

On Days -8, -7, -6, and -5, you will receive busulfan by vein over 2 hours.

On Day -3, you will receive gemcitabine by vein over 4½ hours and then melphalan by vein over 30 minutes.

On Day -2, you will receive melphalan by vein over 30 minutes.

On Day -1, you will rest (you will not receive chemotherapy).

On Day 0, you will receive your stem cells by vein over about 30-60 minutes.

You will receive 3 more doses of palifermin by vein over 15-30 seconds on Days 0, +1, and +2.

As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your skin 1 time each day starting on Day +5 until your blood cell levels return to normal.

Length of Study:

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are released from the hospital, you will continue as an outpatient in the Houston area to be monitored for infections and transplant-related complications.

You will be taken off study about 100 days after the transplant. You may be taken off study early if the disease gets worse, if intolerable side effects occur, if you are unable to follow study directions, or if you choose to leave the study early.

If for any reason you want to leave the study early, you must talk to the study doctor. It may be life-threatening to leave the study after you have started to receive the study drugs but before you receive the stem cell transplant because your blood cell counts will be dangerously low.

Follow-Up:

About 100 days after the transplant:

* You will have a physical exam.
* Blood (about 4 teaspoons) and urine will be collected for routine tests and to check your kidney and liver function.
* If the doctor thinks it is needed, you will have a computed tomography (CT) and/or positron emission tomography (PET) scan to check the status of the disease.
* If the doctor thinks it is needed, you will have a bone marrow aspiration and biopsy to check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

This is an investigational study. Belinostat, busulfan, and rituximab are FDA approved and commercially available for the treatment of lymphoma. Gemcitabine is FDA approved and commercially available for the treatment of breast cancer, non-small cell lung cancer (NSCLC), ovarian cancer, and pancreatic cancer. Melphalan is FDA approved and commercially available for the treatment of multiple myeloma (MM). Azacitidine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). The use of these study drugs in combination to treat lymphoma is considered investigational.

Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.

Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma

For purpose of dose-finding, "toxicity" defined as any of the following events occurring within 30 days from the start of Belinostat infusion :

1. any grade 4 or 5 non-hematologic toxicity, or
2. any grade 3 or 4 mucositis, or
3. any grade 3 or 4 skin toxicity lasting \> 5 days at peak severity

Optimal dose defined as that for which the posterior mean of Pr(toxicity within 30 days \| dose) given the current data is closest to 0.30.

Treatment related mortality (TRM100), defined as death due to any cause without disease recurrence within 100 days post stem cell transplant (SCT).

Mouth and Tooth Diseases

Digestive System Diseases

Stomatitis

Mucositis

Esophagitis

Gastroenteritis

Gastrointestinal Diseases

Mouth Diseases

Stomatognathic Diseases

Esophageal Diseases

Anti-Infective Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.

Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.

mTOR Inhibitor Patient Group: Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Placebo

mTOR Inhibitor Patient Group - Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit.

Questionnaires

Aung Naing, MD

The goal of this clinical research study is to learn if glutamine can help control and prevent sores, blisters, or inflammation in your mouth or esophagus due to your current treatment.

In this study, glutamine will be compared to a placebo. A placebo is not a drug. It looks like the drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. You will have an equal chance of being assigned to either group:

* If you are in Group 1, you will receive glutamine.
* If you are in Group 2, you will receive a placebo.

Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

Study Drug Administration:

Glutamine or the placebo will be taken as a sugary drink by mouth. You will take the drink twice daily starting the day you first receive your anti-cancer therapy or radiation treatment.

You will mix one scoop of powder with 25-100 milliliters (about 2-6 tablespoons) of water. If you are in the chemotherapy group, you will swish the drink for 10 seconds and swallow. If you are in the radiation group, you will swallow the drink in small amounts several times.

Study Visits:

At every visit, you will be asked about any side effects you may be having and about any other drugs you may be taking.

Chemotherapy Group:

On Days 1, 8, and 22 of Cycle 1:

* You will have a mouth exam.
* Your weight will be recorded.

On Day 15 of Cycle 1:

* You will have a mouth exam.
* Your weight will be recorded.
* You will complete a quality of life questionnaire.

On Day 1 of Cycle 2 and beyond:

* You will have a mouth exam.
* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.
* You will complete a quality of life questionnaire.
* You will complete a survey about how you feel about the study drug. This should take about 5-10 minutes to complete.
* If the doctor thinks it is needed, you will have a photograph of your mouth taken.

After 3 months of chemotherapy:

* You will complete a quality of life questionnaire.

After 6 months of chemotherapy:

* Your weight will be recorded.
* You will complete a quality of life questionnaire.

Follow-Up:

For your follow-up questionnaires at Day 1 of every Cycle, at 3 and 6 months, and during the End-of-Study visit, you may be called by the study team. This call should last about 5-10 minutes.

Radiation Therapy Group:

On Weeks 1, 2, 4, and 6 of Radiation:

* You will be asked if you have inflammation of your esophagus.
* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.

On Weeks 3 and 5 of Radiation:

* You will be asked if you have inflammation of your esophagus.
* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.
* You will complete a quality of life questionnaire.
* You will complete a survey about how you feel about the study drug.

On Week 7 of Radiation:

* You will be asked if you have inflammation of your esophagus.
* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.
* You will complete a quality of life questionnaire.
* You will complete a survey about how you feel about the study drug.

  1 month after your radiation has ended:
* You will be asked if you have inflammation of your esophagus.
* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.
* You will complete a quality of life questionnaire.
* You will complete a survey about how you feel about the study drug.

  3 months after your radiation has ended:
* You will complete a quality of life questionnaire.

Follow-Up:

For your follow-up questionnaires at 1 and 3 months and during the End-of-Study visit, you may be called by the study team. This call should last about 5-10 minutes.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest.

You will continue taking the glutamine or placebo for 4 weeks after the completion of your anti-cancer therapy or radiation treatment. If you stop chemotherapy or radiation before completion of the intended study period, you will continue to take the study drug for 4 weeks.

If you develop severe sores, blisters, or inflammation in your mouth or esophagus, you will be removed from the study, and the doctor will give you another medication for your sores and blisters.

Your participation on the study will be over 6 months after completion of your therapy.

End-of-Study Visit:

After you are off study, you will have an end-of-study visit. For the radiation group, this will be 6 months after radiation therapy. For the chemotherapy group, this is 4 weeks after the last dose.

* Your weight will be recorded.
* If the doctor thinks it is needed, blood (about 2 teaspoons) will be drawn for routine tests.
* You will complete a quality of life questionnaire.
* If you are in the chemotherapy group, you will have a mouth exam.

This is an investigational study. Glutamine is FDA approved and commercially available for the treatment of short bowel syndrome. Its use to treat mouth sores and inflammation of the esophagus is investigational.

Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.

Randomized Trial of Glutamine in Patients With Mucositis or Esophagitis

Randomized, Double Blinded Placebo-Controlled Study of Glutamine in Patients With Oral Mucositis on an mTOR Inhibitor-based Regimen or Esophagitis on a Regimen Receiving Radiation to the Esophagus

For esophagus radiation participants, the severity of esophagitis will be taken as the highest grade observed by week six. Wilcoxon rank sum test used to compare the ordered categories of esophagitis severity.

For mTOR inhibitor patients, the severity of oral mucositis will be taken as the maximum grade observed during the 6-month study period. Wilcoxon rank sum test used to compare the ordered categories of mucositis severity.

The Quality of Life assessed by the MD Anderson Symptom Inventory for head and neck cancer (MDASI-HN). The 13 Core symptoms include dry mouth, fatigue, pain, disturbed sleep, drowsiness, feeling of being distressed, anorexia, sadness, numbness/tingling, dyspnea, difficulty remembering, nausea, and vomiting. The 9 Head and Neck symptoms include mouth sores, problems with taste, constipation, teeth/gum problems, skin pain, difficulty with voice, choking/coughing, difficulty swallowing, and problems with mucus specific to head and neck cancers. Total symptom severity include 24 core and Head and Neck symptoms together. Symptom interference asks patients about how their symptoms impact their daily functions. The severity of each symptom and symptom interference is rated on a numerical scale from 0 (symptom is absent) to 10 (worst possible severity)." Higher scores indicate a greater symptom burden.

Participants in each arm received at least 60% of planned doses of the study drug (glutamine or placebo).

Proportion of participants who were free of Mucositis at 18.3 weeks..

Investigators recorded weight at baseline to the end of treatment with glutamine/placebo. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test.

Investigators recorded the weight at baseline and the end of the study. Weight loss calculated at each study assessment visit using the Wilcoxon rank sum test.

CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo.

CTCAE version 4.03 used to access the adverse events. Grade 1 Asymptomatic; clinical or diagnostic observations only; intervention not indicated Grade 2 Symptomatic; altered eating/swallowing; oral supplements indicated Grade 3 Severely altered eating/swallowing; tube feeding, TPN or hospitalization indicated. Total toxicity-evaluable is the total number of participants who had at least one dose of glutamine or placebo

Healios Oncology Nutrition

Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.

Questionnaire completion for Radiation Therapy to Esophagus Patient Group: At baseline, Week 3, 4, 5, and 7 of radiation, and at end of study visit.

Radiation Therapy to Esophagus Patient Group - Glutamine

Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day radiation therapy to the esophagus received. Participant to swallow the drink in small amounts several times.

Questionnaire completion for Radiation Therapy to Esophagus Patient Group: At baseline, Week 3, 4, 5, and 7 of radiation, and at end of study visit.

Radiation Therapy to Esophagus Patient Group - Placebo

Glutamine taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Questionnaires: Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit.

mTOR Inhibitor Patient Group - Glutamine

Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Questionnaires: Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit.

mTOR Inhibitor Patient Group - Placebo

Participants receive placebo beginning on Day 1 of an mTOR inhibitor based therapy. Placebo taken as a sugary drink by mouth. Participant will take the drink twice daily starting first day anti-cancer therapy received. Participant to swish the drink for 10 seconds and swallow. Four weeks of treatment constitute 1 cycle for participants on mTOR inhibitor therapy.

Questionnaire completion for mTOR Inhibitor Patient Group: At baseline, Day 1 of cycle 2 and beyond, after 6 months of chemotherapy, and at end of study visit.

Esophageal

Head & Neck

Lung

Cancer Type

Data were unavailable for 1 participant who withdrew consent after randomization but before treatment start in mTOR Inhibitor Patient Group-Placebo

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma	NCT01983969	Advanced Cancer... Lymphoma	Azacitidine Vorinostat Gemcitabine Busulfan Melphalan Dexamethasone Caphosol Glutamine Pyridoxine Rituximab	15 Years - 65 Years	M.D. Anderson Cancer Center
Carfilzomib/SAHA Combined With High-Dose Gemcitabine/Busulfan/Melphalan With Autologous Stem Cell Transplant in Myeloma	NCT02114502	Myeloma	Carfilzomib SAHA Gemcitabine Busulfan Melphalan Stem Cell Trans... Palifermin Dexamethasone Caphosol Glutamine Pyridoxine	18 Years - 65 Years	M.D. Anderson Cancer Center
Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma	NCT02701673	Lymphoma	Busulfan Caphosol Glutamine Pyridoxine Belinostat Azacitidine Gemcitabine Melphalan Stem Cell Trans...	15 Years - 65 Years	M.D. Anderson Cancer Center
Belinostat Combined With Azacitidine/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Refractory or Relapsed Lymphoma	NCT02701673	Lymphoma	Busulfan Caphosol Glutamine Pyridoxine Belinostat Azacitidine Gemcitabine Melphalan Stem Cell Trans...	15 Years - 65 Years	M.D. Anderson Cancer Center
Randomized Trial of Glutamine in Patients With Mucositis or Esophagitis	NCT01952847	Advanced Cancer...	Placebo Glutamine Questionnaires	17 Years -	M.D. Anderson Cancer Center
Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype	NCT02589145	Lymphoma	Lenalidomide Vorinostat Gemcitabine Busulfan Melphalan Rituximab Dexamethasone Caphosol Glutamine Pyridoxine Enoxaparin Stem Cell Trans... Palifermin	15 Years - 65 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for resource

Every month we try and update this database with for resource cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for resource

Every month we try and update this database with for resource cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for resource cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.