Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 to 69 NCI CALGB-59909 CALGB-59909, NCT00020943

Objectives

1. Determine the two-year progression-free survival of patients with mantle cell lymphoma treated with intensive chemotherapy and rituximab with autologous peripheral blood stem cell (PBSC) transplantation.
2. Determine the complete and partial response rates of patients treated with this regimen.
3. Determine the disease-free and overall survival of patients treated with this regimen.
4. Determine the autologous immune reconstitution in patients treated with this regimen.
5. Determine the feasibility of this regimen in this patient population.
6. Determine whether treatment with rituximab during autologous PBSC transplantation reduces the amount of contaminating lymphoma in the autologous PBSC product.

Entry Criteria

Disease Characteristics:

• Histologically confirmed mantle cell lymphoma



• Presenting with at least one of the following:
  • Coexpression of CD20 (or CD19) and CD5 and a lack of CD23 expression by immunophenotyping
  • Positive for cyclin D1 by immunostaining
  • Presence of t(11,14) by cytogenetic analysis
  • Molecular evidence of bcl-1/IgH rearrangement



• Stage I-IV disease
  • Stage III or IV if nodular histology mantle cell lymphoma present
  • Any stage for other mantle cell histologies
  • No mantle zone histology



• No active CNS disease
  • No symptomatic meningeal lymphoma
  • No known CNS parenchymal lymphoma
  • Lumbar puncture showing mantle cell lymphoma allowed



• Bidimensionally measurable disease greater than 1 cm
  • Nonmeasurable disease includes the following:
    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Inflammatory breast disease
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
    • Lesions in a previously irradiated area

Prior/Concurrent Therapy:

Biologic therapy:

• No more than 1 prior dose of rituximab

Chemotherapy:

• No more than 1 prior cycle of chemotherapy
• At least 3 weeks since prior chemotherapy
• No other concurrent chemotherapeutic agents

Endocrine therapy:

• No chronic use of oral corticosteroids for ongoing medical condition
• No concurrent hormonal therapy except for non-lymphoma-related conditions (e.g., insulin for diabetes)
• Other concurrent corticosteroids for adrenal failure, diffuse alveolar hemorrhage, carmustine pneumonitis, or as an anti-emetic allowed

Radiotherapy:

• No prior radiotherapy for mantle cell lymphoma
• Concurrent palliative radiotherapy allowed
• Concurrent cranial radiotherapy for asymptomatic meningeal lymphoma allowed

Surgery:

• At least 2 weeks since prior major surgery

Patient Characteristics:

Age:

• 18 to 69

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Hepatitis B surface antigen and hepatitis C antibody positive patients must meet all of the following criteria:
  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • AST no greater than 3 times ULN
  • Liver biopsy shows no greater than grade 2 fibrosis and no cirrhosis

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• LVEF at least 45% by MUGA or echocardiogram

Other:

• No known hypersensitivity to murine products
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

At least 45 patients will be accrued for this study within 2 years.

Outline

This is a multicenter study.

Patients receive induction therapy comprising rituximab IV over 4-6 hours on day 1; methotrexate IV over 4 hours on day 2; cyclophosphamide IV over 2 hours, doxorubicin IV, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients also receive leucovorin calcium IV every 6 hours beginning on day 3 and continuing until blood levels of methotrexate are safe. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

Induction therapy repeats every 21-28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Rituximab may be omitted during course 1 if circulating mantle cells are excessive. Patients may receive a third course if more than 15% persistent bone marrow involvement is documented.

Patients with stable or responding disease begin consolidation therapy 29 days after the start of the final course of induction therapy. Patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 96 hours on days 1-4. Patients also receive rituximab IV over 4-6 hours on days 5 or 6 and 12 or 13 and G-CSF SC beginning on day 14 and continuing until leukapheresis is complete. Patients undergo leukapheresis beginning between days 22-25 and continuing until adequate CD34 cells are collected.

Beginning 4 weeks after recovery from consolidation therapy, patients receive high-dose therapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover.

After blood counts recover and more than 35 days after autologous PBSC transplantation, patients receive rituximab IV over 4-6 hours weekly for 2 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 10 years.

Hsi E, Jung S, Lai R, et al.: Ki67 and PIM1 expression in aggressively treated mantle cell lymphoma (MCL): A Cancer and Leukemia Group B (CALGB) 59909 correlative science study. [Abstract] J Clin Oncol 26 (Suppl 15): A-8560, 2008.

Damon LE, Johnson J, Niedzwiecki D, et al.: Immuno-chemotherapy (IC) and autologous stem cell transplant (ASCT) for untreated patients (pts) with mantle cell lymphoma (MCL): CALGB 59909. [Abstract] Blood 108 (11): A-2737, 2006.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Lloyd Damon, MD, Protocol chair		Ph: 415-353-2737; 800-888-8664

Registry Information
Official Title		A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma
Trial Start Date		2001-06-15
Registered in ClinicalTrials.gov		NCT00020943
Date Submitted to PDQ		2001-05-09
Information Last Verified		2004-09-03
NCI Grant/Contract Number		U10-CA31946

Back to Top