Lymphoma
Conditions
Keywords
contiguous stage II mantle cell lymphoma, noncontiguous stage II mantle cell lymphoma, stage I mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma
Brief summary
RATIONALE: To evaluate the efficacy of a new high intensity chemotherapy regimen with thalidomide maintenance in patients with newly diagnosed mantle cell lymphoma 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 rituximab in combination with methotrexate, doxorubicin, cyclophosphamide, leucovorin, vincristine, ifosfamide, etoposide, cytarabine and mesna (MACLO/IVAM) 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: During cycle 1, patients will receive rituximab intravenous (IV), granisetron IV, decadron IV, doxorubicin IV bolus, vincristine intravenous pyelogram (IVP) on day 1; cyclophosphamide IV on day 1-5; vincristine IVP on day 8; methotrexate IV, methotrexate by continuous infusion, then leucovorin IV until methotrexate level is below 0.01 nanomolar (nM) on day 10. Patients will receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 13 and continuing until blood counts recover. When absolute neutrophil count (ANC) reaches1,500/mm\^3, patients will start cycle 2. Patients will receive rituximab IV on day 1; cytarabine IV on day 1 and 2; ifosfamide IV, mesna IV, etoposide IV on day 1-5; and G-CSF SC daily beginning on day 7 and continuing until ANC is greater than 1,000 cells/mm\^3. Approximately 2-3 weeks later, patients receive another course of therapy as above.After cycle 4, patients in complete remission will take oral thalidomide until progression of disease. 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 or at study termination. PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.
Interventions
DRUGRituximab
Rituximab 375 mg/m2 IV, Days 1 of all cycles
DRUGCyclophosphamide
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.
DRUGCytarabine
Cytarabine 2 grams/m2 IV every 12 hours x 4 doses, Days 1 and 2, Cycles 2 and 4.
DRUGDoxorubicin
Doxorubicin 45 mg/m2 IV bolus, Day 1, Cycles 1 and 3
DRUGEtoposide
Etoposide 60 mg/m2 IV daily x 5 days, Cycles 2 and 4
DRUGIfosfamide
Ifosfamide 1.5 grams/m2 IV once a day (QD) x 5 days, Cycles 2 and 4
DRUGLeucovorin
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.
DRUGMethotrexate
Methotrexate 1,200 mg/m2 in 250 cc 5 percent dextrose in water (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.
DRUGThalidomide
Maintenance therapy.
DRUGVincristine
Vincristine 1.5 mg/m2 IVP (maximum of 2 mg), Day 1 and 8 , Cycles 1 and 3.
DRUGMesna
Mesna 360 mg/m2 IV every 3 hours x 5 days, Cycles 2 and 4
G-CSF 480 mcg subcutaneous (SQ) starting Day 13 (Cycles 1 and 3), Day 7 (Cycles 2 and 4)
DRUGGranisetron
Granisetron 1 mg IV on Day 1, Cycle 1 and 3
DRUGDecadron
Decadron 10 mg IV on Day 1, Cycles 1 and 3
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously untreated, histologically confirmed mantle cell lymphoma. * Measurable or evaluable disease. * All stages are eligible. * Age \> 18 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. * Adequate hepatic function: * Bilirubin \< 3 mg/dL. * Transaminases (SGOT and/or SGPT) \< than 2.5 times the upper limit of normal for the institution, unless due to lymphomatous involvement. * Serum creatinine \< 1.5 mg/Dl. * Ability to give informed consent. * Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study. * Life expectancy greater than 6 months.
Exclusion criteria
* Previous chemotherapy, immunotherapy or radiotherapy for this lymphoma * Concurrent active malignancies, with the exception of in situ carcinoma of the cervix and basal cell carcinoma of the skin. * Grade 3 or 4 cardiac failure and/or ejection fraction \< 50. * Psychological, familial, sociological or geographical conditions that do not permit treatment and/or medical follow-up required to comply with the study protocol. * Patients with a known history of HIV or AIDS * Presence of hepatitis or hepatitis B virus (HBV) infection * Pregnant or breast-feeding women. * Central nervous system (CNS) involvement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate | Up to 5 years | Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate | Up to 5 years | Percentage of participants who are alive up to five years after receipt of protocol therapy. |
| Response Rate | Up to 5 years | Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement. |
| Number of Patients Experiencing Adverse Events. | Up to 5 years | Number of patients experiencing adverse events during the course of protocol therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| R-MACLO-IVAM-T Rituximab, Methotrexate, Doxorubicin, Cyclophosphamide and Vincristine (cycle 1), followed by Rituximab, Ifosfamide (and Mesna), Etoposide and Cytarabine (cycle 2). These two cycles are repeated once, and patients achieving complete repose receive maintenance Thalidomide. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | R-MACLO-IVAM-T |
|---|---|
| Age, Continuous | 56.5 years |
| Age, Customized 50 - 59 years | 8 participants |
| Age, Customized < 50 years | 6 participants |
| Age, Customized 60 - 69 years | 5 participants |
| Age, Customized 70 - 79 years | 3 participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 22 / 22 | 22 / 22 | 19 / 20 |
| serious Total, serious adverse events | 21 / 22 | 21 / 22 | 19 / 20 |
Outcome results
Primary
Progression-free Survival Rate
Percentage of participants achieving progression-free survival at 1, 3 and 5 years after the start of protocol therapy, based upon the International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL). Progression is defined as a ≥ 50% increase from nadir in the product of the two largest perpendicular diameters (PPD-size) of any previously identified abnormal node, or appearance of any new lesion.
Time frame: Up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-MACLO-IVAM-T | Progression-free Survival Rate | 1 year progression-free survival | 91 percentage of participants |
| R-MACLO-IVAM-T | Progression-free Survival Rate | 3 year progression-free survival | 78 percentage of participants |
| R-MACLO-IVAM-T | Progression-free Survival Rate | 5-year progression-free survival | 69 percentage of participants |
Secondary
Number of Patients Experiencing Adverse Events.
Number of patients experiencing adverse events during the course of protocol therapy.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-MACLO-IVAM-T | Number of Patients Experiencing Adverse Events. | 22 participants |
| R-IVAM Cycles | Number of Patients Experiencing Adverse Events. | 22 participants |
| Thalidomide Therapy | Number of Patients Experiencing Adverse Events. | 19 participants |
Secondary
Overall Survival Rate
Percentage of participants who are alive up to five years after receipt of protocol therapy.
Time frame: Up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-MACLO-IVAM-T | Overall Survival Rate | 4-year overall survival rate | 87 percentage of participants |
| R-MACLO-IVAM-T | Overall Survival Rate | 5-year overall survival rate | 87 percentage of participants |
| R-MACLO-IVAM-T | Overall Survival Rate | 1-year rate overall survival Rate | 96 percentage of participants |
| R-MACLO-IVAM-T | Overall Survival Rate | 2-year overall survival Rate | 96 percentage of participants |
| R-MACLO-IVAM-T | Overall Survival Rate | 3-year overall survival rate | 96 percentage of participants |
Secondary
Response Rate
Percentage of participants achieving complete response (CR) to protocol therapy according to International Working Group Response Criteria for Non-Hodgkin's Lymphoma (NHL) using the CT imaging method. Patients were classified by best tumor response; CR was defined as normalization of the lactate dehydrogenase (LDH), complete disappearance of disease-related symptoms and lymph nodes, and clearance of lymphoma from involved organs; complete response unconfirmed (CRu) as a residual lymph node greater than 1.5 cm in greatest transverse diameter that had regressed by more than 75% or an indeterminate bone marrow examination; partial response (PR) as greater than 50% reduction in the involved lymph nodes, or disappearance of the involved lymph nodes but persistent bone marrow involvement; relapse/progression as new or increased lymph nodes, organomegaly, or reappearance of bone marrow involvement.
Time frame: Up to 5 years
Population: Participants who completed at least two cycles of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-MACLO-IVAM-T | Response Rate | 100 percentage of participants |