Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Recurrence

Lymphoma

Leukemia

Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Leukemia, Prolymphocytic

Leukemia, Prolymphocytic, T-Cell

Disease Progression

Waldenstrom Macroglobulinemia

Leukemia, Plasma Cell

Leukemia, Prolymphocytic, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Disease Attributes

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Leukemia, B-Cell

Chronic Disease

Leukemia, T-Cell

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

T-cell Prolymphocytic Leukemia

Plasma Cell Leukemia

B Cell Prolymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Amino Acids

Etoposide

Cytarabine

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Melphalan

Mycophenolic Acid

Tacrolimus

Etoposide phosphate

Podophyllotoxin

Carmustine

Mechlorethamine

Nitrogen Mustard Compounds

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimetabolites

Enzyme Inhibitors

Antiviral Agents

Calcineurin Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Keratolytic Agents

Tubulin Modulators

Antimitotic Agents

Phenylalanine

Alanine

Allogeneic Bone Marrow Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation

Autologous Hematopoietic Stem Cell Transplantation

Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Mycophenolate Mofetil

Peripheral Blood Stem Cell Transplantation

Total-Body Irradiation

Mohamed Sorror

This phase II trial studies autologous peripheral blood stem cell transplant followed by donor bone marrow transplant in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia. Autologous stem cell transplantation uses the patient's stem cells and does not cause graft versus host disease (GVHD) and has a very low risk of death, while minimizing the number of cancer cells. Peripheral blood stem cell (PBSC) transplant uses stem cells from the patient or a donor and may be able to replace immune cells that were destroyed by chemotherapy. These donated stem cells may help destroy cancer cells. Bone marrow transplant known as a nonmyeloablative transplant uses stem cells from a haploidentical family donor. Autologous peripheral blood stem cell transplant followed by donor bone marrow transplant may work better in treating patients with high-risk Hodgkin lymphoma, non-Hodgkin lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

PRIMARY OBJECTIVES:

I. Event-free survival (EFS) at 1-year after autograft.

SECONDARY OBJECTIVES:

I. Relapse rates at 1-year after autograft.

II. Overall survival (OS) at 1-year after autograft.

III. Incidence of grades II-IV acute GVHD and chronic extensive GVHD.

IV. Non-relapse mortality (NRM) at 200 days and 1 year after allograft.

V. Donor engraftment at day +84.

VI. Incidence of infections.

OUTLINE:

CONDITIONING REGIMEN 1 (lymphoma, Waldenstrom macroglobulinemia, or chronic lymphocytic leukemia \[CLL\] with no dose limiting radiation or significant comorbidities: Patients receive cyclophosphamide intravenously (IV) on days -6 and -5. Patients undergo high-dose total body irradiation (TBI) twice daily (BID) on days -3 to -1.

CONDITIONING REGIMEN 2 (lymphoma, Waldenstrom Macroglobulinemia, CLL, with prior dose-limiting radiation, or significant comorbidities): Patients receive carmustine IV on day -7, etoposide IV BID on days -6 to -3, cytarabine IV BID on days -6 to -3, and melphalan IV on day -2.

CONDITIONING REGIMEN 3 (multiple myeloma or plasma cell leukemia, with no significant renal insufficiency or other significant comorbidities): Patients receive high-dose melphalan IV on day -2.

CONDITIONING REGIMEN 4 (multiple myeloma or plasma cell leukemia, with significant renal insufficiency or other significant comorbidities): Patients receive lessened dose of melphalan IV on day -2.

PBSC TRANSPLANTATION: All patients undergo autologous PBSC transplantation on day 0.

WAITING INTERVAL: Between 40 and 120 days.

NONMYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV once daily (QD) on days -6 to -2 and cyclophosphamide IV QD on days -6 to -5 and day 3. Patients infused with donor's peripheral blood stem cells will additionally receive cyclophosphamide IV on day 4. Patients undergo low-dose TBI on day -1.

ALLOGENEIC BONE MARROW TRANSPLANTATION: Patients undergo donor bone marrow transplantation on day 0.

GRAFT VERSUS HOST DISEASE PROPHYLAXIS: Beginning on day 4, patients receive tacrolimus orally (PO) or IV and taper beginning on day 86 if no graft-versus-host disease. Patients also receive mycophenolate mofetil PO thrice daily (TID) on days 4 - 35.

PERIPHERAL BLOOD COUNT SUPPORT: Patients receive filgrastim (G-CSF) IV or subcutaneously (SC) beginning from day 4 and continue till blood counts recover.

ALLOGENEIC PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) TRANSPLANTATION: Patients undergo donor PBMC transplantation on day 0.

GRAFT VERSUS HOST DISEASE PROPHYLAXIS: Beginning on day 5, patients receive tacrolimus orally (PO) or IV and taper beginning on day 86 if no graft-versus-host disease. Patients also receive mycophenolate mofetil PO thrice daily (TID) on days 5 - 35.

PERIPHERAL BLOOD COUNT SUPPORT: Patients receive filgrastim IV or SC beginning from day 5 and continue till blood counts recover.

After completion of study treatment, patients are followed up annually for 5 years.

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

Sequential Autologous HCT / Nonmyeloablative Allogeneic HCT Using Related, HLA-Haploidentical Donors for Patients With High-Risk Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

Number of patients surviving without relapsed/progressive disease

Relapse/Progression defined as:

Nodes, liver, and/or spleen ≥50% increased or new by physical exam / imaging studies.

Circulating lymphocytes ≥50% increased by morphology and/or flow cytometry. Richter's transformation by lymph node biopsy .

Number of patients surviving one year post-autograft

aGVHD The diagnosis of aGVHD is identified through various stages and grading of the disease related to Skin (Rash), Gut (Diarrhea, Nausea/vomiting and/or anorexia) and the liver (Bilirubin) assessed by severity and grading scale outlined in the section Grafts vs Hosts by Sullivan (1999).

GVHD Grades Grade I: 1-2 Skin Rash; No gut or liver involvement Grade II: Stage 1-3 Skin rash; Stage 1 gut and/or stage 1 liver involvement Grade III: Stage 2-4 gut involvement and/or stage 2-4 liver involvement with or without rash Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

CGVHD The diagnosis of cGVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.

Number of patients with non-relapse mortalities.

Number of patients with donor engraftment.

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Allogeneic Bone Marrow Transplantation: Undergo donor HCT

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo donor HCT

Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSC transplant

Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation: Undergo autologous-donor tandem HCT

Carmustine: Given IV

Cyclophosphamide: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative study

Melphalan: Given IV

Mycophenolate Mofetil: Given PO

Peripheral Blood Stem Cell Transplantation: Undergo donor HCT

Tacrolimus: Given IV or PO

Total-Body Irradiation: Undergo TBI

Treatment (Autologous HCT, Donor HCT)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Mohamed L. Sorror

Event-Free Survival (EFS)

Number of Patients With Relapsed/Progressive Disease

Overall Survival

Acute Graft-versus-Host-Disease

Chronic extensive Graft-versus-Host-Disease

Two patients are not evaluable for Graft-versus-Host-Disease due to disease progression; they failed the study and did not receive the allogeneic transplantation.

Number of Patients With Grade II-IV Acute Graft-versus-Host-Disease and/or Chronic Extensive Graft-versus-Host-Disease

200 days

1 Year

Two patients are not evaluable for GVHD due to disease progression; they failed the study and did not receive the allogeneic transplantation.

Non-relapse Mortality (NRM)

Number of Patients Who Engrafted

Number of Patients Who Had Infections

Overall Study

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Neoplasm Metastasis

Syndrome

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Neoplasms

Communicable Diseases

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Philadelphia Chromosome

Preleukemia

Myelodysplastic Syndromes

Histiocytosis, Langerhans-Cell

Histiocytosis

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Langerhans Cell Histiocytosis

Rituximab

Thymoglobulin

Busulfan

Thiotepa

Clofarabine

Antilymphocyte Serum

Antineoplastic Agents, Immunological

Myeloablative Regimen: Rituxan 375 mg/m\^2 (B cell malignancy) by vein (IV) on Day -10; Busulfan AUC 4,000 IV either as an outpatient prior to admission or as an inpatient on Day -9; Clofarabine 30 mg/m\^2 IV Day -7 to Day -4; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; Fludarabine 10 mg/m\^2 IV on Days -7 to -4; Total Body Irradiation (TBI) 2 Gy on Day -3; with Cord Blood infusions on Day 0.

Reduced Intensity: Fludarabine 40 mg/m\^2 IV on Days -5 to -2; Melphalan 140 mg/m\^2 IV on Day -2; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; with Cord Blood infusions on Day 0.

140 mg/m2 by vein on Day -2 only for Fludarabine + Melphalan group.

10 mg/m2 by vein on Days -7 to -4 for Melphalan + Thiotepa + Fludarabine group, or 40 mg on Days -5 to -2 for Fludarabine + Melphalan group.

15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth twice a day from Days -3 to +100 in the absence of Graft vs Host Disease (GvHD).

Mycophenolate mofetil

Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no Graft vs Host Disease (GvHD) is present.

Cord blood infusion on Day 0. Each participant will receive cells from one unexpanded cord blood sample plus cells from a second cord blood sample that has undergone fucosylation.

Cord Blood Infusion

375 mg/m\^2 by vein on Day -10 for B cell malignancy.

1.25 mg/Kg by vein on Day -4.

1.75 mg/Kg by vein on Day -3.

Busulfan per standard of care, test dose either as an outpatient prior to admission or as an inpatient on Day -9. Busulfan pharmacokinetics performed with test dose and the first dose on Day -7 per standard of care. Doses of Days -5 and -4 subsequently adjusted to target an AUC of 4,000 microMol.min-1.

Total Body Irradiation (TBI)

Elizabeth Shpall, MD

The goal of this clinical research study is to learn if it is safe and feasible to transplant changed cord blood for patients with leukemia or lymphoma. Researchers also want to learn if this can help to control the disease.

The cord blood will be changed to make use of sugar that is found in small amounts in blood cells. It plays a role in signaling where in the body the transplanted cells should go to. Adding more sugars to the cord blood cells in the laboratory is designed to help the cord blood cells find their way faster to the bone marrow. This may help your blood counts to recover faster. This process is called fucosylation.

Anti-thymocyte globulin (ATG) is a protein that removes immune cells that cause damage to the body.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's bone marrow cells.

Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells to die.

Mycophenolate mofetil (MMF) and tacrolimus are designed to block the donor cells from growing and spreading in a way that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue attacks the recipient's body). This may help to prevent GVHD.

Rituximab is designed to attach to cancer cells, which may cause them to die.

Central Venous Catheter Placement:

You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for it.

The chemotherapy, some of the other drugs in this study, and the cord blood transplant will be given by vein through your CVC. Blood samples will also be drawn through your CVC. The CVC will remain in your body for about 2-5 months.

Study Plans:

If you agree to take part in this study, your doctor will choose one of the following 2 study plans based on the disease and your age and medical history.

Fludarabine/Clofarabine/Busulfan/Rituximab/Total Body Irradiation:

If you are between 1 and 55 years of age and can receive high-dose chemotherapy, or you are between 55 and 65 years old and your doctor agrees, you will receive fludarabine, clofarabine, busulfan, ATG, total body irradiation, and possibly rituximab.

You will receive a test dose of busulfan by vein over 60 minutes as an outpatient. If the test dose cannot be given as an outpatient, you will be admitted to the hospital on Day -10 for intravenous (IV) fluids and will receive the busulfan test dose on Day -9. This low-level "test" dose of busulfan is to check how the level of busulfan in your blood 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.

About 11 samples of blood will be drawn for pharmacokinetic (PK) testing of busulfan. PK testing measures the amount of study drug in the body at different time points. These blood samples will be drawn at various timepoints starting before the busulfan infusion and continuing over about the next 11 hours. The blood samples will be repeated again with the first day of high-dose busulfan treatment. Each sample will be about 1 teaspoon of blood. A temporary heparin lock 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.

If you will receive the test dose as an outpatient, you will be admitted to the hospital on Day -8 and will receive fluids by vein. If appropriate for the disease, you will receive rituximab by vein over 4-6 hours on Day -8.

If you will receive the test dose as an inpatient, you will be admitted on Day -10 and will receive fluids by vein. If appropriate for the disease, you will receive rituximab by vein over 4-6 hours on Day -10.

On Days -7 through -4, you will receive fludarabine by vein over 1 hour, clofarabine by vein over 1 hour, and busulfan by vein over 3 hours. You will receive ATG on Days -4 and -3. On Day -3, you will receive a single treatment of low-dose total body irradiation. You will "rest" (not receive chemotherapy drugs) on Days -2 and -1. Day 0 is the day of the cord blood transplant, so the negative day numbers are used to label the treatment days before the transplant.

All chemotherapy drugs, fluids, and other drugs that must be given by vein will be infused through the catheter. Once the back-up cells are collected, all participants will be admitted to the hospital as indicated by their assigned treatment plan schedule.

Fludarabine/Melphalan:

If your doctor chooses fludarabine and melphalan, you will have the following schedule:

* On Day -6 (6 days before your transplant), you will be admitted to the hospital and will receive fluids by vein.
* On Days -5, -4, and -3, you will receive fludarabine by vein over 30 minutes.
* On Days -4 and -3, you will receive ATG by vein over 4 hours.
* On Day -2, you will receive fludarabine by vein over 30 minutes and melphalan by vein over 30 minutes.
* On Day -1, you will not receive any drugs.
* On Day 0, you will receive your cord blood transplant through the CVC.

Supportive Drugs:

Starting on Day -3, you will receive mycophenolate mofetil as a tablet by mouth 2 times a day. If you are not able to take the tablet by mouth, you will receive MMF by vein over 2 hours 2 times a day. If you do not have GVHD at Day 100 after your cord blood transplant, the dose of MMF will be gradually lowered. If you have GVHD, MMF may be stopped 7 days after the GVHD is controlled.

Starting on Day -2, you will receive tacrolimus by vein as a continuous (nonstop) infusion until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 6 months. After that, your tacrolimus dose may be gradually lowered if you do not have GVHD. Your doctor will discuss this with you.

Starting on Day 0, you will receive filgrastim (G-CSF) through a needle under the skin 1 time a day every day until your white blood count begins to recover. Filgrastim is designed to help cells in the bone marrow to divide, which helps raise white blood cells counts more quickly, lower fever, and decrease the risk of infection.

Study Visits:

At about 1, 3, 6, and 12 months after the transplant:

* You will have a physical exam.
* You will be checked for possible reactions to the transplant and study drugs, including GVHD.
* Blood (about 4 teaspoons) will be drawn for routine tests, to check for CMV antibodies, and for genetic tests to learn if the donor's cells have "taken". The routine blood tests will be repeated as often as the doctor thinks is needed.
* If the doctor thinks it is needed, you will have a bone marrow aspiration to check the status of the disease.

You will need to stay in the hospital for about 4 weeks. After you leave the hospital, you will continue as an outpatient in the hospital area, which means you will have to stay close enough to be able to come back for any visits for about 100 days after the transplant.

Length of Participation:

You will be on study for up to 1 year. You will be taken off study early if the disease gets worse, if intolerable side effects occur, if the cord blood is infected and cannot be transplanted, if you are unable to follow study directions, or if your doctor thinks it is in your best interest.

This is an investigational study. Fucosylation is not an FDA-approved process. It is currently being used for research purposes only. Fludarabine, busulfan, clofarabine, melphalan, mycophenolate mofetil, tacrolimus, and rituximab are FDA approved and commercially available to be given to patients with leukemia or lymphoma having a cord blood transplant. Total body irradiation is delivered using FDA-approved and commercially available methods.

Up to 50 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies

Engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.

Engraftment date is the first day of three (3) consecutive days that the absolute neutrophil count (ANC) exceeds 0.5 x109/L. Time measured in days.

American Stem Cell, Inc.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia	NCT01008462	B-Cell Prolymph... Hypodiploidy Loss of Chromos... Plasma Cell Leu... Progression of ... Recurrent Adult... Recurrent Adult... Recurrent Child... Recurrent Child... Recurrent Chron... Recurrent Plasm... Recurrent Small... Refractory Chil... Refractory Chro... Refractory Non-... Refractory Plas... Refractory Smal... t(14;16) t(4;14) T-Cell Prolymph... Waldenstrom Mac...	Allogeneic Bone... Allogeneic Hema... Autologous Hema... Autologous-Allo... Carmustine Cyclophosphamid... Cytarabine Etoposide Fludarabine Pho... Laboratory Biom... Melphalan Mycophenolate M... Peripheral Bloo... Tacrolimus Total-Body Irra...	- 75 Years	Fred Hutchinson Cancer Center
Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies	NCT01471067	Blood And Marro... Leukemia Lymphoma Transplantation... Transplantation...	Melphalan Fludarabine Mycophenolate m... Tacrolimus Cord Blood Infu... Rituximab ATG Busulfan Clofarabine Total Body Irra...	1 Year - 80 Years	M.D. Anderson Cancer Center
Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies	NCT01471067	Blood And Marro... Leukemia Lymphoma Transplantation... Transplantation...	Melphalan Fludarabine Mycophenolate m... Tacrolimus Cord Blood Infu... Rituximab ATG Busulfan Clofarabine Total Body Irra...	1 Year - 80 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for hypodiploidy

Every month we try and update this database with for hypodiploidy 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.