Neoplasms

All Conditions

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Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Sarcoma

Soft Tissue Sarcoma

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Liposomal doxorubicin

Molgramostim

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Isophosphamide mustard

Dexrazoxane

Razoxane

Mesna

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Immunologic Factors

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Trace Elements

Antineoplastic Agents, Alkylating

Alkylating Agents

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Pre-Surgery, Regimen 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m\^2/day for 2 days, Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen 1: Methotrexate 12 gm/m\^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m\^2 twice daily, Leucovorin Rescue.

Pre-Surgery, Regimen 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, Regimen 2: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Pre-Surgery, Regimen 1: IV Over 15 Minutes on Day 1 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV on Day 1 of Weeks 16, 21, and 26; Pre-Surgery, Regimen 2: IV over 15 Minutes on Day 1 of Weeks 1, 4, and 7. Dose 90 mg/m\^2.

Pre-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 1 and 6; Post-Surgery, Regimen 1: IV Over 48 Hours, on Days 1 and 2 of Weeks 16, 21, and 26. Pre-Surgery, Regimen 2: Infusion through an artery over 4 hours on Day 1 of Weeks 1, 4, and 7. Dose 60 mg/m\^2/day for 2 days continuous infusion.

Pre-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 4, 5, 9, and 10; Post-Surgery, Regimen 1: IV Over 4 Hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30; Post-Surgery, Regimen 2: IV Over 4 Hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39. Dose 12 gm/m\^2, max 20 gm over 4 hours.

Pre- and Post-Surgery, Regimen 1: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours; Post-Surgery, Regimen 2: IV Over 5 minutes on the day after each methotrexate dose and then by mouth every 6 hours. Dose 10 mg IV, with 10 mg orally every 6 hours.

Dose 900 mg/m\^2 IV Push with doxorubicin. Pre-Surgery, Regimen 2: IV Over 15 minutes on Day 1 of Weeks 1, 4, and 7.

Post-Surgery, Regimen 2: IV continuously over 5 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m\^2. Dose 2.8 grams m\^2/day.

Questionnaires to be completed on 5 different days during the study.

Questionnaire

Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg) twice a day for 7 days on, 7 days off, beginning the day receive gemcitabine.

Planned limb salvage surgery after 3 courses of doxorubicin + cisplatin (IV) and High-dose methotrexate - at approximately week 12.

Surgery

IV continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Dose 2.8 gm/m\^2/day.

Peter M. Anderson, MD, PhD

The goal of this clinical research study is to learn if giving certain combinations of chemotherapy drugs before and after surgery, mostly in the outpatient clinic instead of in the hospital, can result in fewer hospital stays during treatment for osteosarcoma. The drugs and schedules will vary depending on the status of the cancer and its level of risk for spreading, but they will include combinations of doxorubicin (non-liposomal), cisplatin, methotrexate, and ifosfamide, as described below.

The Study Drugs:

The standard treatment combination used to treat patients with osteosarcoma is doxorubicin, cisplatin, and methotrexate with or without ifosfamide. When this treatment combination is given in the hospital, it can require around 18-22 hospital stays. Somewhat recently, chemotherapy for osteosarcoma has become possible to give in the outpatient clinic. Researchers want to learn if giving 4 certain drugs (the combination of doxorubicin, cisplatin, and methotrexate with or without ifosfamide) in the outpatient setting to eligible patients will help to decrease the number of hospital stays.

During this study, all study participants whose tumor(s) can be taken out with surgery will be offered routine surgery to remove the tumor(s). After surgery, if the doctor believes the tumor(s) have responded well enough, the standard treatment combination is again doxorubicin, cisplatin, and methotrexate. If the tumor(s) have not responded well enough, however, the standard treatment combination is methotrexate and ifosfamide.

In this study, participants are considered at "higher risk" for the tumor(s) spreading to the lungs in the following cases: if the participant's tumor(s) are large at the time of joining this study, if the cancer has spread to other organs, and/or if standard chemotherapy in this study has not killed enough tumor cells.

The following drugs are used in this study:

* Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.
* Cisplatin has an atom at its center that contains a type of metal called platinum. The platinum is supposed to poison the cancer cells.
* Methotrexate is designed to disrupt cells (including cancer cells) from making and repairing DNA and "copying" themselves.
* Ifosfamide is designed to stop the growth of cancer cells, which may cause the cells to die.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 groups based on the likelihood that the surgery will be able to control the disease in the arm or leg that has the bone tumor(s).

Group 1 includes participants who are considered to have a "standard" chance that surgery will be able to control the disease in the arm or leg, participants who will have an amputation, or participants with cancer in areas other than in an arm or leg at the time of diagnosis.

Group 2 includes participants who are considered to have a "higher" chance that the tumor(s) will be left behind after having surgery that the doctor considers as "incomplete" to control the disease.

Central Venous Line:

For drugs to be given by vein, your study doctor will likely recommend that you have a central venous line (CVL) placed. A central venous line 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 this procedure.

Pre-Surgery Chemotherapy for Group 1:

Before surgery, Group 1 participants will receive doxorubicin, cisplatin, and methotrexate followed by leucovorin. Leucovorin is given to help prevent and/or treat the side effects that methotrexate may cause. Dexrazoxane is used to decrease the risk of side effects to the heart that doxorubicin may cause. These drugs will be given in an outpatient clinic (without requiring hospitalization), if possible.

Doxorubicin will be given by vein over 15 minutes, after dexrazoxane by vein over 15 minutes, on Day 1 of Weeks 1 and 6.

Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2 of Weeks 1 and 6.

Methotrexate will be given by vein, over 4 hours, on Day 1 of Weeks 4, 5, 9, and 10. If you have difficulty recovering from the effects of the methotrexate therapy, you may only receive methotrexate twice before surgery, instead of 4 times.

Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.

Pre-Surgery Chemotherapy for Group 2:

Before surgery, Group 2 participants will receive dexrazoxane, doxorubicin, and cisplatin.

On Day 1 of Weeks 1, 4, and 7, dexrazoxane will be given by vein over 15 minutes, followed by doxorubicin given by vein over 15 minutes and then cisplatin through an artery over 4 hours. Infusion through an artery requires a hospital stay of 2-4 days.

Surgery:

For all eligible study participants, the surgery to remove the tumor(s) will be performed on either Week 11 or 12. The surgery will be explained to you in detail, and you will be asked to sign a separate consent form for it that will describe its risks.

Before surgery, you will have routine visits with the surgeon. You will have several routine scans performed to help plan the surgery.

Chemotherapy Regimens after Surgery:

After the surgery (on or around Week 14), you will receive additional "post-surgery" chemotherapy.

After surgery, if you were originally in Group 1, and if the doctor believes the tumor(s) have responded well enough (specifically, if 90% or more of the tumor cells are dead when checked under the microscope), you will receive additional chemotherapy that is similar to what you received before surgery. This is described below as Regimen A. If the doctor does not believe the tumor(s) have responded well enough (if less than 90% of the tumor cells are dead when checked under the microscope), however, you will be assigned to Regimen B.

All participants who started in Group 2 will be assigned to Regimen B.

Radiation and Chemotherapy for Patients Ineligible for Routine Surgery:

A small number of participants on this study may need to have radiation therapy to help control the disease, as part of their routine care. This would only be done if the tumor(s) cannot be completely taken out with surgery, or if amputation is necessary but refused by the participant. If needed, and depending on where the tumor(s) are located, your doctor may decide that radiation is needed. All participants needing radiation or having surgery that the doctor considers as "incomplete" to control the disease are considered "higher risk" and will receive Regimen B therapy during and after radiation. (Radiation will usually begin during Weeks 12-14, but it could be anytime during ifosfamide therapy.) The radiation therapy will be explained to you in detail, and you will be asked to sign a separate consent form for it that will describe its risks.

Post-Surgery Chemotherapy for Regimen A:

Regimen A includes the following treatments:

* Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 19, 20, 24, 25, 29, and 30.
* Doxorubicin will be given on Day 1 of Weeks 16, 21, and 26.
* Cisplatin will be given as a continuous infusion by vein over 48 hours, on Days 1 and 2 of Weeks 16, 21, and 26.
* Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.

Post-Surgery Chemotherapy for Regimen B:

Regimen B includes the following treatments:

* Methotrexate will be given over 4 hours on Day 1 of Weeks 14, 15, 20, 21, 26, 27, 32, 33, 38, and 39.
* Leucovorin will be given by vein, over 5 minutes, on the day after each methotrexate dose and then by mouth every 6 hours after that, until the study doctor believes that the methotrexate level in the blood is low. The methotrexate level in the blood will be checked using a blood test (less than 2 teaspoons each time). This test will be performed once a day after each methotrexate infusion, until the methotrexate blood level is low and it is considered safe to stop the leucovorin.
* Ifosfamide will be given by vein, continuously over 5 days each time, on Weeks 16, 22, 28, and 34.
* Mesna will be given by vein, continuously over 6 days each time, on Weeks 16, 22, 28, and 34. Mesna is used to decrease the risk of bleeding in the bladder and kidneys while ifosfamide is taken.

Study Tests:

After Week 5 of treatment, and then again before surgery, you will have the following tests performed:

* Your medical history will be reviewed.
* You will have a physical exam.
* Blood (about 2-3 teaspoons each time) will be collected for routine tests and tests of your kidney and liver function. The routine blood tests may be repeated more often during the weeks you are receiving any of the study drugs.

If you are receiving cisplatin, you may have a hearing test performed before each dose of this drug.

You will have an ECHO performed before your fourth dose of doxorubicin on Week 14, and possibly more often if necessary.

Questionnaires:

You will be asked to complete 5 brief questionnaires on 5 different days during this study. The questionnaires ask about the health-related quality of your life, and include questions about how you have felt, physically and emotionally, during cancer treatment. The questionnaires also ask how you and your family have adapted to your having cancer treatments, and what effects the medicines may have had on whether you have felt healthy or sick.

These questionnaires will be completed at Week 1, at about Week 7 (before surgery or radiation), sometime during Weeks 20-22, at the end-of-treatment visit (either the end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit), and 1 year after your first diagnosis of cancer. It should take you about 15-20 minutes to fill out the questionnaires each time.

External Care:

If the study doctor allows and you agree, some of the blood tests in this study may be performed outside of M. D. Anderson. The study doctor will discuss this option with you, if applicable.

Length of Study Participation:

If the disease gets worse or intolerable side effects occur, you will be taken off study.

End-of-Regimen-A Visit, End-of-Regimen-B Visit, or End-of-Treatment Visit:

If you complete Regimen A or B as planned or you leave the study early for any reason, the following procedures will be performed:

* You will have a physical exam.
* Urine and blood (about 2-3 teaspoons) will be drawn for routine tests and tests of your kidney and liver function.
* You will have an ECHO, x-rays of the disease area and the chest, CT scans of the chest, and a bone scan.
* You will also have whole-body scans and a hearing test.

Follow-Up Visits:

After the end-of-Regimen-A visit, the end-of-Regimen-B visit, or the end-of-treatment visit, you will be asked to return for follow-up visits. At these visits, the following procedures will be performed:

* CT scans of the chest will be performed every 3 months for the first year after your chemotherapy ends, every 4 months for the 2nd year, every 6 months for the 3rd year, and once a year for the next 2 years.
* You will have a bone scan every year for 5 years.

This is an investigational study. All of the drugs used in this study are commercially available and commonly used in osteosarcoma. This study is designed to look at the drugs' use in the outpatient setting, which is considered research.

Up to 40 patients will take part in this study. All will be enrolled at M. D. Anderson.

Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

Outpatient Chemotherapy in Pediatric Osteosarcoma: Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy

Treatment success defined as a patient having 6 or fewer hospitalizations during front-line chemotherapy.

M.D. Anderson Cancer Center

Expected toxicities for these varieties of osteosarcoma chemotherapy.

Pre-Surgery, Group 1: Doxorubicin intravenous (IV) 90 mg daily, Cisplatin 60 mg/m\^2/day for 2 days, Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Surgery; Post-Surgery, Regimen A: Methotrexate 12 gm/m\^2, Doxorubicin IV 90 mg, Cisplatin 60 mg/ m\^2 twice daily, Leucovorin Rescue or Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen B: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Outpatient Chemotherapy

Pre-Surgery, Group 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, all Group 2 assigned to Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days

Additional Risk-Adapted Outpatient Chemotherapy

Pre-Surgery, Group 2: Dexrazoxane 900 mg/m\^2 intravenous (IV) then Doxorubicin IV 90 mg daily, Cisplatin 120 mg/m\^2 (intra-arterial); Surgery; Post-Surgery, all Group 2 assigned to Regimen B: Methotrexate 12 gm/m\^2, Leucovorin Rescue 10 mg IV, with 10 mg orally every 6 hours; Ifosfamide 2.8 grams m\^2/day and Mesna 2.8 gm/m\^2/day continuous IV over 6 days; Lung-Directed Chemotherapy, Regimen 2: Gemcitabine, Sargramostim Inhaled aerosol (5 mcg/kg, maximum dose 300 mcg).

Total

Age, Continuous

Female

Male

Gender

United States

Region of Enrollment

Study could not meet accrual goal due to logistical considerations, terminated early.

Peter M. Anderson, MD, PHD / Professor

Treatment Success (6 or Fewer Hospitalizations During Front-line Chemotherapy)

Quality of Life (Ped QL) Assessment

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Immunoblastic Lymphadenopathy

Lymphoma, Large-Cell, Anaplastic

Enteropathy-Associated T-Cell Lymphoma

Lymphoma, Non-Hodgkin

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Peripheral T-cell Lymphoma

Angioimmunoblastic T-cell Lymphoma

Angioimmunoblastic Lymphadenopathy With Dysproteinemia

Anaplastic Large Cell Lymphoma

Enteropathy-associated T-cell Lymphoma

Subcutaneous Panniculitis-like T-cell Lymphoma

Anti-Inflammatory Agents

Cyclophosphamide

Prednisone

Vincristine

Vorinostat

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Histone Deacetylase Inhibitors

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Up to two 100 mg capsules of Vorinostat (dosage will vary from 100 mg orally (PO) twice daily (BID), 300 mg PO every evening and 200 mg PO BID with the starting dose at 300 mg PO every evening for the phase I trial) are to be administered orally twice daily (once in the morning and once in the evening, or if in the daily dosing cohort once in the evening) in repeated 21-day cycles consisting of 10 days dosing starting on days 5 through 14 followed by a 7-day rest period, during which no vorinostat will be administered.

Zolinza (vorinostat)

750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Yasuhiro Oki, MD

The goal of this clinical research study is to find out how well the drug Zolinza (vorinostat) works in combination with the drug combination called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) to treat patients with untreated T-cell Non-Hodgkin's Lymphoma (NHL). The safety of these drugs in combination and the best dose of vorinostat when given in combination with CHOP will also be studied.

The Study Drugs:

Vorinostat is designed to cause chemical changes in different groups of proteins that are attached to DNA (the genetic material of cells), which may slow the growth of cancer cells or cause the cancer cells to die.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.

Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.

Vincristine is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.

Prednisone is designed to decrease inflammation by preventing white blood cells from completing an inflammatory reaction. This drug can cause lymphocytes, a type of white blood cell, to break apart and die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will begin to take vorinostat on the first day of treatment which is Day -1. Vorinostat capsules are taken by mouth, either 3 times a day or 2 times a day, depending on what the study doctor thinks is in your best interest. If you are taking vorinostat 3 times a day, it should be taken in the morning, afternoon and evening. If you are taking vorinostat 2 times a day, you will take the capsules in the morning and evening. The capsules must be taken with food (within 30 minutes after a meal). You will receive the vorinostat capsules on the first day of each cycle. You will also receive instructions on how to take the drug. You should return any unused vorinostat capsules back to study staff at the end of each cycle. You will take vorinostat for 5 days (Days -1 through 3) of each cycle and then beginning on Day 1, cyclophosphamide, vincristine, and doxorubicin will be given though a needle in your vein. This will happen for each 21-day study cycle. Cyclophosphamide is given over 1 hour. Vincristine is given over 15 minutes. Doxorubicin is also given over 15 minutes.

The starting dose of vorinostat may change On Days 1-5 of each cycle, you will take prednisone tablets by mouth.

If you begin to experience severe or intolerable side effects, the study drug schedule may be stopped for up to 3 weeks. If the side effects improve, you may be able to receive the study drugs again, with either a lower dose of vorinostat or if you are taking vorinostat three times daily, you may take it twice a day instead. The chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine, and prednisone) may also be lowered depending on what side effects are being experienced. If you continue to have severe or intolerable side effects with the lower dose of vorinostat and chemotherapy, you will taken off study.

Study Visits:

On Day 1 of all cycles, the following tests and procedures will be performed:

* Your medical history will be recorded, including any drugs that you are taking.
* You will be asked about any side effects you may have experienced.
* You will have a physical exam, including measurement of your vital signs and weight.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* Your performance status will be recorded.

On Day 1 of Cycle 2 you will have an ECG.

On or before Day 1 of Cycle 3 the following tests and procedures will be performed if your doctor thinks necessary:

* You will have CT and/or PET scans to check the status of the disease.
* You may have a bone marrow aspirate and/or biopsy to check the status of the disease.

Length of Study:

You will receive the study drugs for up to 6 cycles. You may be taken off study early if the disease gets worse or if severe or intolerable side effects occur.

End-of-Study Visit:

If you go off study treatment for any reason, you will have an end-of-study visit within 4 weeks after your last dose of study drugs or before starting a new treatment. At this visit, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded.
* You will be asked about any side effects you may have experienced.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* You will have CT scans and PET scans to check the status of the disease.
* If you had skin lesions when you began the study, the skin lesions will be photographed.
* If the doctor thinks it is needed, you will have bone marrow biopsy and/or aspirate.

Follow-up Visits:

After you are off study treatment, you will have follow-up visits. You will go to these visits every 3 months for the1st year, every 4 months for the 2nd and 3rd years, and every 6 months for the 4th and 5th years. After this, you will return 1 time each year unless the lymphoma returns. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs.
* Your performance status will be recorded
* You will be asked about any side effects you may have experienced.
* Blood (about 5 teaspoons) will be drawn for routine tests.
* You will have CT scans and PET scans to check the status of the disease.
* If you had skin lesions when you began the study, the skin lesions will be photographed.
* If the doctor thinks it is needed, you will have bone marrow biopsy and/or aspirate.

This is an investigational study. Vorinostat is FDA approved and commercially available for the treatment of cutaneous T-cell lymphoma that has not come back or not responded to prior therapy. CHOP is currently FDA approved for treatment of patients with NHL. The use of vorinostat in combination with CHOP in patients with T-cell NHL is investigational.

Up to 52 patients will take part in this study. All will be enrolled at MD Anderson.

SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma

A Phase I/II of Vorinostat Plus CHOP in Untreated T-cell Non-Hodgkin's Lymphoma

MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); and for Phase II Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).

MTD of Vorinostat defined as highest dose level in which 6 patients have been treated with less than 2 instances of DLT. Continual reassessment during each 21-day cycle to assess DLT. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle. The dose of Vorinostat escalated in successive 3+3 cohorts of participants to determine the MTD.

MTD of Vorinostat when administered in combination with Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) defined as highest dose level in which 6 patients have been treated with less than 2 instances of dose limiting toxicity (DLT). Continual reassessment during each 21-day cycle to assess dose limiting toxicity. Two schedules of Vorinostat were investigated: Phase I A) daily doses on days 5 to 14, or Phase II B) three times a day on days -2 to 3 of standard CHOP every 21 days. Vorinostat was administered orally on days 5 to 14 (Schedule A), first at 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), and next at 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle); Schedule B Vorinostat administered orally 300 mg orally three times daily from days -2 to 3 (4500 mg over 5 days per cycle).

Merck Sharp & Dohme LLC

Phase I: Vorinostat administered Days 5 to 14 at starting dose 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle), next administered dose 200 mg orally twice daily (4000 mg over 10 days per cycle).

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 21 day cycle: Doxorubicin 50 mg/m\^2 IV Day 1; Prednisone 100 mg tablets orally/day Days 1-5; Cyclophosphamide 750 mg/m\^2 IV Day 1; Vincristine 1.4 mg/m\^2 IV Day 1.

Schedule A: Vorinostat Once or Twice Daily

Phase II: Vorinostat administered at starting dose 300 mg orally three times daily from Days -2 to 3 (4500 mg over 5 days per cycle).

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 21 day cycle: Doxorubicin 50 mg/m\^2 IV Day 1; Prednisone 100 mg tablets orally/day Days 1-5; Cyclophosphamide 750 mg/m\^2 IV Day 1; Vincristine 1.4 mg/m\^2 IV Day 1.

Schedule B: Vorinostat Three Times Daily

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin : 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Prednisone : 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Zolinza (vorinostat) : Starting oral dose (Schedule A) of 300 mg once a day on Days 5-14 of 21 day cycle.

Cyclophosphamide : 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Zolinza + CHOP

Sex: Female, Male

300 mg once daily on Days 5 to14

200 mg twice daily on Days 5 to14

300 mg three times daily on Days -2 to 3

Number of participants who received either Vorinostat treatment Schedule A (300 mg once daily or 200 mg twice daily) for Phase I or Schedule B (300 mg three times daily) for Phase II.

Vorinostat Treatment (Schedule A/Schedule B)

Yasuhiro Oki, MD/ Associate Professor

Vorinostat 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle) on Days 5-14 of 21 day cycle or Vorinostat 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle) on Days 5-14 of 21 day cycle

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin : 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Prednisone : 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Cyclophosphamide : 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Schedule A - Vorinostat Once or Twice Daily

Phase I Maximum Tolerated Dose (MTD) of Vorinostat

Vorinostat 300 mg orally once daily (total doses of 3000 mg over 10 days per cycle) on Days 5-14 of 21 day cycle

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin : 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Prednisone : 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Cyclophosphamide : 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Schedule A - Vorinostat Once Daily

Vorinostat 200 mg orally twice daily (total doses of 4000 mg over 10 days per cycle) on Days 5-14 of 21 day cycle

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin : 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Prednisone : 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Cyclophosphamide : 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Schedule A - Vorinostat Twice Daily

Number of Participants With Dose Limiting Toxicity for Determination Phase I (Schedule A) MTD of Vorinostat

Vorinostat administered orally 300 mg three times daily from days -2 to 3 (4500 mg over 5 days per cycle) of 21 day cycle.

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin : 50 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Prednisone : 100 mg tablets by mouth once a day on Days 1-5 of 21 day cycle

Cyclophosphamide : 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Schedule B - Vorinostat Three Times Daily

Phase II MTD of Vorinostat

Zolinza (vorinostat) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)

Doxorubicin: 50 mg/m\^2 by vein/intravenous (IV) over 15 minutes on Day 1 of 21 day cycle

Prednisone: 100 mg tablets by mouth/orally (PO) once a day on Days 1-5 of 21 day cycle

Zolinza (vorinostat): Phase I Starting dose of 300 mg by mouth each evening on Days 5-14 of 21 day cycle.

Cyclophosphamide: 750 mg/m\^2 by vein over 1 hour on Day 1 of 21 day cycle

Vincristine : 1.4 mg/m\^2 by vein over 15 minutes on Day 1 of 21 day cycle

Doxorubicin 17.5 mg/m\^2 IV bolus infusion, followed by continuous IV infusion on days 1-4. Radiation treatments 5 days a week for 6 - 6 1/2 weeks. 60 Gy in 6 weeks (negative resection margin) to 66 Gy in 6.5 weeks (positive resection margin).

17.5 mg/m\^2 IV bolus infusion, followed by continuous IV infusion on days 1-4.

Radiation treatments 5 days a week for 6 - 6 1/2 weeks. 60 Gy in 6 weeks (negative resection margin) to 66 Gy in 6.5 weeks (positive resection margin).

Radiation Therapy

Peter W. Pisters, MD

The goal of this clinical research study is to learn if the combination of radiation therapy plus low dose doxorubicin chemotherapy given after surgery is effective in the treatment of sarcoma. The safety of this treatment will also be studied.

Doxorubicin is a drug that is commonly used to treat certain kinds of cancer.

The radiation treatment and chemotherapy will start around 4-6 weeks after surgery. During the study, you will receive radiation treatments 5 days a week for 6 - 61/2 weeks. On Day 1 of each week of radiation therapy, you will be given doxorubicin through a continuous injection into a vein for 4 days in a row. A special tube is placed into a large vein in the neck or chest region or through a large vein in the arm. This is called a central venous line. A small pump is then used to give the drug. This pump is about the size of a pack of cigarettes. You will receive appropriate instructions for the maintenance of the pump. The doxorubicin and radiotherapy will be given on an outpatient basis at M. D. Anderson.

If the disease gets worse or you experience any intolerable side effects, chemotherapy and/or radiation therapy may be stopped and you may be taken off the study. At that time, your doctor will discuss other treatment options with you.

Before the start of each week of treatment, you will have a physical exam and blood tests (around 2 tablespoons). You will also have a MRI to check on the status of the disease.

After the study, you will have follow-up visits at M. D. Anderson every 3-4 months for the first 2 years after the study then every 6 months for the next 3 years. After that you will have follow-up visits once a year for the rest of your life to check on the status of the disease. At every follow-up visit you will have ultrasound scans. You will have a MRI at the first follow-up visit then only when the doctor feels it is necessary.

This is an investigational study. Doxorubicin is FDA approved and is commercially available. Up to 30 patients will take part in this study. All will be enrolled at M. D. Anderson.

Post-Operative Chemoradiation for Extremity & Trunk Soft Tissue Sarcoma

A Phase I Study of Post-Operative Concurrent Chemoradiation for Extremity and Trunk Soft Tissue Sarcoma

Toxicity defined by acute local toxicity to skin and subcutaneous tissues and delayed wound healing. Toxicity defined as (1) grade 3 or 4 myelosuppression with fever or (2) grade 3 or 4 desquamation, or (3) both (1) and (2), scored within 6 weeks from the start of doxorubicin treatment.

Behaviors and Mental Disorders

Lymphoma, B-Cell

Aggression

B-cell Lymphoma

Antiemetics

Gastrointestinal Agents

Dexamethasone

Cytarabine

Rituximab

Dexamethasone acetate

BB 1101

Antineoplastic Agents, Immunological

Antiviral Agents

R-HCVAD + R-MTX/Ara-C ((Rituximab-HCVAD (rituximab, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) alternating with Rituximab-Methotrexate-Cytarabine))

R-CHOP ((Rituximab-CHOP (Rituximab, cyclophosphamide, vincristine, and prednisone))

No longer recruiting for this study arm.

Arm A: Rituximab 375 mg/m² by vein on day 1, Cycle 1 and alternating cycles. Arm B: Rituximab 375 mg/m² on day 1, Cycle 2 and alternating cycles.

Arm A: Cyclophosphamide 300 mg/m\^2 by vein (IVPB) over 3 hours every 12 hours x 6 doses on Days 2-4, Cycle 1 and alternating cycles.

Arm B: Cyclophosphamide 750 mg/m² by vein day 1

Arm A: Doxorubicin 50 mg/m\^2/day by vein over 15 minutes (12 hours after last dose of cyclophosphamide) on Day 5, Cycle 1 and alternating cycles.

Arm A: Vincristine 1.4 mg/m\^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12, Cycle 1 and alternating cycles.

Arm B: Vincristine 1.4 mg/m\^2 (maximum 2 mg) by vein (IVPB) on Days 5 (1-24 hours after last cyclophosphamide) and on day 12 of each cycle.

Arm A: Dexamethasone 40 mg by vein or by mouth daily x 4 on Days 2-5 and on days 12-15 of cycle 1 and alternating cycles.

Arm A: Methotrexate after finishing Rituximab, 200 mg/m2 by vein over 2 hours, then 800 mg/m2 by vein over 22 hours day 1 cycle 2.

Arm B: Cytarabine 3 g/m\^2 by vein over 2 hours every 12 hours X 4 doses on days 3 \& 4, cycle 2 and alternating cycles.

Arm B: Prednisone 100 mg by mouth (as a pill, capsule, or tablet) once a day on Days 1-5, each cycle.

Luis E. Fayad, MD

The overall goal of this clinical research study was to find out which of two different chemotherapy drug combinations, R-CHOP and R-HCVAD, is more effective in treating B-cell lymphoma.

At this point, all participants will now be assigned to the R-HCVAD arm of the study. Researchers will study the safety and effectiveness of this drug combination.

This study originally involved 2 different study drug regimens, R-CHOP and R-HCVAD. R-CHOP is made up of rituximab, cyclophosphamide, vincristine, and prednisone, and is the most common treatment for patients with non-Hodgkin's lymphoma. This combination was compared with R-HCVAD, which is made up of rituximab, doxorubicin, cyclophosphamide, vincristine, and dexamethasone.

Rituximab (Rituxan®) is a humanized monoclonal antibody against cluster of differentiation antigen 20 (CD20) (a receptor in the surface of malignant B-cell lymphocytes). The drug has activity against aggressive and nonaggressive NHL of B-cell origin, and has been used in combination with chemotherapy. Cyclophosphamide is a type of drug know as an alkylating agent. Vincristine is a type of drug called vinca alkaloids. It is typically used in lymphomas, leukemias, and other tumors. Prednisone is a type of steroid. Dexamethasone is a steroid that may have activity against lymphomas. Methotrexate is an anti-cancer drug and a folic acid antagonist. It is used to treat solid tumors, lymphomas, leukemias, and autoimmune diseases.

When this study began, participants were randomly assigned (as in the flip of a coin) to 1 of 2 arms: Arm A (R-HCVAD alternating with a combination of rituximab, methotrexate, and Ara-C) or Arm B (R-CHOP). From this point on, all new participants will be treated with the Arm A combination, which has shown to be better.

If you are found to be eligible to take part in this study, you will be given the study drugs in 21-day cycles. The cycles will alternate between R-HCVAD and a combination of rituximab, methotrexate, and Ara-C. During Cycle 1 (the R-HCVAD cycle), you will receive rituximab through a needle in your vein (intravenously, or "IV"), on Day 1. The infusion will take about 1 hour. Cyclophosphamide will be given by IV every 12 hours for 3 days. Each infusion of cyclophosphamide will take about 3 hours. Doxorubicin will be given as a 15-minute infusion on Day 5 with the supervision of a nurse. Your doctor may also choose to give you the doxorubicin over 24-48 hours using a small pump that you will carry around your waist in a "fanny pack." You will not have to stay in the hospital to receive this study drug. Vincristine will be given by IV, on Days 5 and 12. Each vincristine infusion will take about an hour. Dexamethasone will be given by mouth (as a pill, capsule, or tablet) on Days 2-5 and 12-15. You will also be given other standard medications to help prevent possible side effects of these medications (such as nausea, vomiting, or rash).

In Cycle 2 (the rituximab-methotrexate-Ara-C cycle), you will receive rituximab on Day 1. You will receive methotrexate by IV (after finishing the rituximab) on Days 2 and 3. The infusion will take about 24 hours. You will be given a small "fanny pack" with a pump inside that will slowly infuse the drug. You do not have to stay in the hospital while the drug is being given. You will be given Ara-C every 12 hours on Days 3-4 (a total of 4 doses). You will be given other standard medications to help prevent possible side effects of these medications (such as nausea, vomiting, or rash) during this cycle also.

Leucovorin is given 12 hours after each methotrexate infusion. It is used to stop the action of the methotrexate and to prevent/lessen any side effects that the methotrexate may cause.

During treatment, you will have blood draws (between 2-3 tablespoons) every week for routine tests. Every 4 weeks during treatment , you will be asked questions about your medical history and have a physical exam to check for any side effects. Every 2 cycles (about every 8 weeks), you will have bone marrow biopsies performed (if they were positive before starting on this study), until they come back negative. You will have a positron emission tomography (PET) scan to see if the tumor is responding. Once the PET scan comes back negative, it will be up to your physician to decide if you need additional PET scan tests, and when. You will have CT scans of the chest, abdomen, pelvis, and neck every 2 cycles, if they were positive at the beginning of the study also. You may have additional testing done while on this study, if your physician feels that it is needed (for example, if it is needed to check for side effects).

You may receive additional medication called "CNS prophylaxis" before receiving the study treatments. Your doctor will discuss these medications with you. The "CNS prophylaxis" consists of an alternating dose of either doxorubicin or methotrexate. The methotrexate will be given either by IV pump or by a "lumbar puncture" (a needle inserted into the space between the vertebrae in your back to infuse the drug directly into the spinal area). The doxorubicin will be given by IV. Changes in the dose level of CNS prophylaxis will be approved if you are at risk for or are experiencing serious side effects.

You will receive the study drugs for up to 6-8 cycles on an outpatient basis. This means you will not have to be admitted to the hospital to receive the study drugs. You may be taken off study if the disease gets worse. If you experience intolerable side effects while taking any of the study drugs, your study doctor may decide to delay your treatment for up to 3 weeks (one study cycle) or to continue your therapy on the drugs at a lower dose. If the side effects become very severe, your doctor may decide to take you off of the study and stop the medication.

At the end of your scheduled treatments, you will be asked to return to the clinic for follow-up visits every 6 months for the first, second, third, and fourth year after treatment on this study. You will then be followed every year after that. If your doctor feels it is necessary, you may have blood tests (about 3-5 teaspoons) performed at these visits. You will have bone marrow biopsies every other year for the first 2 years, if they were positive before you started on this study, and then every year after that. At these visits, you will be asked about any side effects you may have experienced and whether or not your cancer has come back. If your doctor feels there is a chance that the cancer has come back, he or she may schedule x-rays or scans in order to check. You will also be asked about any other therapies you may be having to treat your cancer, if it has come back.

If you are taken off study for any reason, you will be asked to come back to the clinic for an end-of-treatment visit within 4 weeks from the last treatment. This visit will include a physical exam, routine blood tests (about 5-8 teaspoons), a blood-pregnancy test for women who are able to get pregnant, an ECG, and a chest x-ray.

This is an investigational study. All of the study drugs are approved by the FDA for the treatment of lymphoma. Up to 66 patients will take part in this study. All of the patients will be enrolled at MD Anderson.

Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger

A Phase II Randomized Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Doxorubicin With Cisplatin, High-Dose Methotrexate, and Additional Risk-Adapted Outpatient Chemotherapy	NCT00673179	Osteosarcoma	Doxorubicin Cisplatin Methotrexate Leucovorin Dexrazoxane Ifosfamide Questionnaire Gemcitabine Sargramostim Surgery Mesna	5 Years - 40 Years	M.D. Anderson Cancer Center
SAHA + CHOP in Untreated T-cell Non-Hodgkin's Lymphoma	NCT00787527	Lymphoma	Zolinza (vorino... Cyclophosphamid... Doxorubicin Vincristine Prednisone	18 Years -	M.D. Anderson Cancer Center
Post-Operative Chemoradiation for Extremity & Trunk Soft Tissue Sarcoma	NCT00502411	Soft Tissue Sar...	Doxorubicin Radiation Thera...	-	M.D. Anderson Cancer Center
Study of Rituximab-HCVAD Alternating With Rituximab-Methotrexate-Cytarabine Versus Standard Rituximab-CHOP Every 21 Days for Patients With Newly Diagnosed High Risk Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients 60 Years Old or Younger	NCT00290498	Lymphoma	Rituximab Cyclophosphamid... Doxorubicin Vincristine Dexamethasone Methotrexate Cytarabine Prednisone	16 Years - 60 Years	M.D. Anderson Cancer Center
Bortezomib With Gemcitabine/Doxorubicin in Patients With Urothelial Cancer and Other Solid Tumors	NCT00479128	Solid Tumor Urethral Cancer	Bortezomib Gemcitabine Doxorubicin	-	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for hydroxydaunomycin hydrochloride