Rituximab and Combination Chemotherapy Followed By Thalidomide in Treating Patients With Previously Untreated Mantle Cell Lymphoma
Overview[ - collapse ][ - ]
| Purpose | RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as thalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with combination chemotherapy and thalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma. |
|---|---|
| Condition | Lymphoma |
| Intervention | Drug: Rituximab Drug: Cyclophosphamide Drug: Cytarabine Drug: Doxorubicin Drug: Etoposide Drug: Ifosfamide Drug: Leucovorin Drug: Methotrexate Drug: Thalidomide Drug: Vincristine Drug: Mesna Drug: Filgrastim (G-CSF) |
| Phase | Phase 2 |
| Sponsor | University of Miami Sylvester Comprehensive Cancer Center |
| Responsible Party | University of Miami Sylvester Comprehensive Cancer Center |
| ClinicalTrials.gov Identifier | NCT00450801 |
| First Received | March 20, 2007 |
| Last Updated | August 13, 2013 |
| Last verified | August 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | March 20, 2007 |
|---|---|
| Last Updated Date | August 13, 2013 |
| Start Date | April 2004 |
| Estimated Primary Completion Date | April 2014 |
| Current Primary Outcome Measures | Progression-free survival at 6, 12, 18, and 24 months [Time Frame: 6, 12, 18, and 24 months] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Not Provided |
Descriptive Information[ + expand ][ + ]
| Brief Title | Rituximab and Combination Chemotherapy Followed By Thalidomide in Treating Patients With Previously Untreated Mantle Cell Lymphoma |
|---|---|
| Official Title | Phase II Study of Rituximab in Combination With Methotrexate, Doxorubicin, Cyclophosphamide, Leucovorin, Vincristine, Ifosfamide, Etoposide, Cytarabine and Mesna (Maclo/Ivam) in Patients With Previously Untreated Mantle Cell Lymphoma |
| Brief Summary | RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as thalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with combination chemotherapy and thalidomide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients with previously untreated mantle cell lymphoma. |
| Detailed Description | OBJECTIVES: Primary - Determine the progression-free survival of patients with previously untreated mantle cell lymphoma treated with rituximab and combination chemotherapy comprising vincristine, doxorubicin hydrochloride, cyclophosphamide, methotrexate, ifosfamide, cytarabine, and etoposide followed by thalidomide. Secondary - Determine the overall survival of patients treated with this regimen. - Determine the response rate in patients treated with this regimen. - Determine the toxicity of this regimen in these patients. OUTLINE: Patients receive rituximab IV and doxorubicin hydrochloride IV over 3-5 minutes on day 1, vincristine IV on days 1 and 8, cyclophosphamide IV over 30 minutes on days 1-5, methotrexate IV over 24 hours on day 10, and leucovorin calcium IV every 6 hours beginning on day 11 and continuing until the level of methotrexate in the blood is within a safe range. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover. When absolute neutrophil count (ANC) reaches 1,500/mm^3, patients receive rituximab IV on day 1 (i.e., the day ANC reaches 1,500/mm^3), ifosfamide IV over 1 hour on days 1-5, cytarabine IV over 3 hours every 12 hours on days 1 and 2, and etoposide IV over 1 hour on days 1-5. Patients also receive G-CSF SC once daily beginning on day 7 and continuing until blood counts recover. Approximately 2-3 weeks later, patients receive another course of therapy as above. Patients in complete remission after 2 courses of rituximab and combination chemotherapy receive oral thalidomide daily. Treatment with thalidomide continues for 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed monthly for 3 months, every 3 months for 2 years, every 6 months for 3-5 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study. |
| Study Type | Interventional |
| Study Phase | Phase 2 |
| Study Design | Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition | Lymphoma |
| Intervention | Drug: Rituximab Rituximab 375 mg/m2 IV, Days 1, 4 Cycles Other Names: RituxanDrug: Cyclophosphamide Cyclophosphamide 800 mg/m2 IV, Day 1, Cyclophosphamide 200 mg/m2 IV Days 2 - 5, Cycles 1 and 3. Cyclophosphamide will be given in 100 cc NS IV over 30 minutes. Other Names: CytoxanDrug: Cytarabine Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4. Other Names: AraCDrug: Doxorubicin Doxorubicin 45 mg/m2 IV bolus, DAy 1, Cycles 1 and 3 Other Names: AdriamycinDrug: Etoposide Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4 Other Names: VP16Drug: Ifosfamide Ifosfamide 1.5 grams/m2 IV QD x 5 days, Cycles 2 and 4 Other Names: IfexDrug: Leucovorin Leucovorin 180 mg/m2 IV beginning 36 hours after start of methotrexate infusion and then 12 mg/m2 IV every 6 hours until methotrexate level is below 0.01 nM. Day 10, Cycles 1 and 3. Other Names: Folinic AcidDrug: Methotrexate Methotrexate 1,200 mg/m2 in 250 cc D5W IV over 1 hour followed by Methotrexate 5,520 mg/m2 in 1,000 cc D5W by continuous infusion over 23 hours (240 mg/m2 every hour for 23 hours). Day 10, Cycles 1 and 3. Other Names: amethopterinDrug: Thalidomide Maintenance therapy. Other Names: ThalomidDrug: Vincristine Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 8 , Cycles 1 and 3. Other Names: OncovinDrug: Mesna Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4 Other Names: MesnexDrug: Filgrastim (G-CSF) G-CSF 480 mcg SQ starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4) Other Names: Neupogen |
| Study Arm (s) | Experimental: MACLO IVAM |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 22 |
| Estimated Completion Date | April 2014 |
| Estimated Primary Completion Date | April 2014 |
| Eligibility Criteria | Inclusion Criteria: DISEASE CHARACTERISTICS: - Histologically confirmed mantle cell lymphoma - All stages allowed - Previously untreated disease - Measurable or evaluable disease - No CNS involvement PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Life expectancy > 6 months - Bilirubin < 3 mg/dL - SGOT and/or SGPT < 2.5 times upper limit of normal (unless due to lymphomatous involvement) - Creatinine < 1.5 mg/dL - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective double-method contraception during and for ≥ 4 weeks after completion of study treatment (if receiving thalidomide) - No other concurrent active malignancies, except for in situ carcinoma of the cervix or basal cell carcinoma of the skin Exclusion Criteria: Grade 3-4 cardiac failure - LVEF that is less than ≥ 50% - psychological, familial, sociological, or geographical conditions that would preclude study compliance - known history of HIV or AIDS - hepatitis or hepatitis B virus infection PRIOR CONCURRENT THERAPY: - Any prior chemotherapy, immunotherapy, or radiotherapy for this lymphoma |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT00450801 |
|---|---|
| Other Study ID Numbers | UMIAMI-20030165 |
| Has Data Monitoring Committee | Yes |
| Information Provided By | University of Miami Sylvester Comprehensive Cancer Center |
| Study Sponsor | University of Miami Sylvester Comprehensive Cancer Center |
| Collaborators | Not Provided |
| Investigators | Study Chair: Izidore S. Lossos, MD University of Miami Sylvester Comprehensive Cancer Center |
| Verification Date | August 2013 |
Locations[ + expand ][ + ]
| University of Miami Sylvester Comprehensive Cancer Center - Miami | Miami, Florida, United States, 33136 |
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