Combination Chemotherapy in Treating Patients With Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: Filgrastim (G-CSF)Biological: Bleomycin Sulfate (BLM)Biological: Recombinant Interferon AlfaProcedure: Peripheral Blood Stem Cell TransplantationRadiation: Radiation Therapy
- Registration Number
- NCT00002835
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy in treating patients who have intermediate-grade or immunoblastic lymphoma.
- Detailed Description
OBJECTIVES:
* Compare the efficacy of early intensification vs alternating triple chemotherapy in patients with intermediate-grade or immunoblastic lymphoma with poor prognostic features.
* Compare, in a prospective manner, the cost/benefit ratio of these regimens in these patients.
* Determine the value of monitoring minimal residual disease detection via in vitro culture methods and polymerase chain reaction analysis of peripheral stem cell apheresis products and by longitudinal monitoring of blood and bone marrow samples in these patients treated with these regimens.
OUTLINE: This is a randomized study. Patients are stratified according to tumor score (3 or 4 vs 5 or 6).
During the first course of induction, patients receive IDSHAP comprising idarubicin (IDA) and cisplatin IV continuously on days 1-4, cytarabine (ARA-C) IV over 2 hours on day 5, and methylprednisolone (MePRDL) IV over 15 minutes on days 1-5. During the second course of induction, patients receive MBIDCOS comprising vincristine, bleomycin, and cyclophosphamide IV over 15 minutes on day 1, IDA IV continuously and MePRDL IV over 15 minutes on days 1-3, methotrexate (MTX) IV over 2 hours on day 10, and oral leucovorin calcium every 6 hours on days 11 and 12. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity.
Patients with stable or responding disease after induction are randomized to 1 of 2 treatment arms.
Arm I
* Patients receive the following 3 courses of early intensification.
* First course: Patients receive ifosfamide (IFF) IV continuously and etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover and then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest.
* Second course: Patients receive IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in the first course.
* Third course: Patients receive carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity.
Arm II
* Patients receive IDSHAP during courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Each course lasts 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients with residual disease after completion of arm I or II treatment undergo radiotherapy to areas of bulk disease if feasible. Patients on both arms with meningeal involvement receive ARA-C intrathecally (IT) alternated with MTX every other day until 1 week after clearing of CNS disease and then 2 IT injections during every course of chemotherapy thereafter. Patients with divergent histology who achieve complete response after completion of arm I or II treatment receive interferon alfa 3 times a week for 1 year.
Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and then annually for 2 years.
PROJECTED ACCRUAL: A maximum of 136 patients will be accrued for this study within 4 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I Filgrastim (G-CSF) 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm I Cytarabine (ARA-C) 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm I Melphalan 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm I Peripheral Blood Stem Cell Transplantation 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm II Bleomycin Sulfate (BLM) IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Recombinant Interferon Alfa IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Cisplatin (CDDP) IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Radiation Therapy IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Leucovorin Calcium IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Peripheral Blood Stem Cell Transplantation IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm I Etoposide (VP-16) 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm II Vincristine Sulfate IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm I mitoxantrone hydrochloride (DHAD) 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm I Carmustine 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm I Ifosfamide 3 courses of early intensification: First course: Ifosfamide (IFF) IV continuously and Etoposide (VP-16) IV over 2 hours every 12 hours on days 1-3. Filgrastim (G-CSF) administered subcutaneously (SC) beginning on day 5 and continuing until blood counts recover then autologous peripheral blood stem cells (PBSC) are harvested, selected for CD34 positive cells, and purged in vitro. If more than 5% of the WBC contains lymphoma cells after induction, then 2 courses of IFF and VP-16 are administered before PBSC harvest. Second course: IFF IV continuously on days 1-3, mitoxantrone (DHAD) IV on day 1, and G-CSF SC as in first course. Third course: Carmustine IV over 1 hour on day -6, ARA-C and VP-16 IV every 12 hours on days -5 to -2, and melphalan IV on day -1. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Each course lasts 3 weeks in the absence of disease progression or unacceptable toxicity. Arm II Cyclophosphamide IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Methotrexate IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Idarubicin IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7. Arm II Methylprednisolone IDSHAP during 4 week courses 2 and 5, MBIDCOS during courses 3 and 6, and IFF and VP-16 IV over 1 hour on days 1-3 and DHAD IV over 15 minutes on day 1 during courses 1, 4, and 7.
- Primary Outcome Measures
Name Time Method Efficacy of Early Intensification vs. Alternating Triple Chemotherapy Monthly
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States