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

Alternate Title

Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed Under 70 NCI CALGB-109901 CALGB-109901, NCT00006252

Objectives

1. Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic peripheral blood stem cell transplantation, in terms of 6-month treatment-related mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia, low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.
2. Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
3. Determine the time to disease progression in patients responding to this regimen.
4. Determine the percentage of donor chimerism achieved in patients treated with this regimen.
5. Determine the risk of acute and chronic graft-versus-host disease in patients treated with this regimen.
6. Determine the toxic effects of this regimen in these patients.
7. Determine the overall survival and disease-free survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• One of the following histologically confirmed diagnoses:
  • Chronic lymphocytic leukemia
    • Absolute lymphocytosis greater than 5,000/mm³
    • Morphologically mature lymphocytes with less than 55% prolymphocytes
    • Lymphocyte phenotypic expression of CD19 and CD5
    • Failed at least 1 prior regimen
      • Progressive lymphocytosis with more than 50% increase in peripheral lymphocytosis or a progressive lymph node or spleen enlargement (at least 25% enlargement or the appearance of new lymph nodes) that persists for at least 4 weeks despite concurrent or prior drug treatment

      OR

    • At least 1 of the following high-risk factors and not in first complete remission
      • 17p deletion
      • 11q deletion
      • Unmutated VH gene status
      • p53 mutations
  • Prolymphocytic leukemia (PLL)
    • Absolute lymphocytosis greater than 5,000/mm³
    • Morphologically mature lymphocytes with more than 55% prolymphocytes
  • Low-grade non-Hodgkin's lymphoma
    • Small lymphocytic lymphoma
    • Follicular center lymphoma (grade I or II)
    • Diffuse (predominately small cell type)
    • Marginal zone, B-cell lymphoma
    • No transformed lymphoma
    • Failure of at least 1 prior regimen

      OR

    • At least 3 of the following risk factors:
      • Over 60 years of age
      • Performance status greater than 1
      • LDH greater than normal
      • More than 1 site of extranodal disease
      • Disease stage III or IV
  • Mantle cell lymphoma
    • Any stage
    • Ineligible for protocol CALGB-59908
    • At least 1 prior treatment regimen
    • At least 1 of the following:
      • Immunophenotypic expression of CD5 and CD19 and absence of CD23
      • Cytogenetic analysis with presence of t(11;14)
      • Overexpression of cyclin D1
      • Rearrangement of BCL1 gene



• Responsive or stable disease to most recent prior therapy
  • Prior therapy for PLL not required



• Must have HLA identical sibling (6/6) donor by serologic typing (A, B, DR)
  • No syngeneic donors
  • No age restriction

 [Note: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

Prior/Concurrent Therapy:

Biologic therapy:

• No prior autologous transplantation

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy

Surgery:

• At least 4 weeks since prior surgery

Patient Characteristics:

Age:

• Under 70

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 500/mm³*
• Platelet count at least 50,000/mm³*

 [Note: *Unless attributable to disease]

Hepatic:

• Bilirubin no greater than 3 times upper limit of normal (ULN)*
• AST no greater than 3 times ULN*

 [Note: *Unless attributable to disease]

Renal:

• Creatinine clearance at least 40 mL/min, unless attributable to disease

Cardiovascular:

• LVEF at least 30% by MUGA

Pulmonary:

• DLCO greater than 40%
• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No uncontrolled diabetes mellitus
• No active serious infection
• No known hypersensitivity to E. coli-derived products

Expected Enrollment

A maximum of 45 patients will be accrued for this study.

Outcomes

Treatment-related mortality within the first 6 months post-transplant

Complete response at 1 year
Percentage of patients achieving complete donor chimerism or mixed donor chimerism at day 90 post-transplant
Disease control

Outline

This is a multicenter study.

Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover.

Patients with no signs of active graft-versus host disease and stable or progressive disease receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.

Patients are followed every 3 months for 2 years and then every 6 months for 5 years.

Shea TC, Johnston J, Walsh W, et al.: Reduced intensity allogeneic transplantation provides high disease-free and overall survival in patients (pts) with advanced indolent NHL and CLL: CALGB 109901. [Abstract] Blood 110 (11): A-486, 2007.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Thomas Shea, MD, Protocol chair		Ph: 919-966-7746 Email: sheaT@med.unc.edu

Registry Information
Official Title		Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma with Allogeneic Donor Stem Cells
Trial Start Date		2001-02-05
Registered in ClinicalTrials.gov		NCT00006252
Date Submitted to PDQ		2000-07-19
Information Last Verified		2006-05-18
NCI Grant/Contract Number		CA31946

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