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

Alternate Title

Donor Stem Cell Transplant in Treating Patients With Relapsed Hematologic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed Under 70 NCI CALGB-100002 NCT00053196

Objectives

1. Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell transplantation by demonstrating that the risk of treatment-related mortality during the first 6 months is an acceptable rate of less than 40% in patients with relapsed hematologic malignancies after prior high-dose chemotherapy and autologous stem cell transplantation.
2. Determine the response rates (disease-specific partial and complete response) in patients treated with this regimen.
3. Determine the 6-month and 12-month probabilities of response in patients treated with this regimen.
4. Determine the distribution of time-to-progression in patients responding to this regimen.
5. Determine the percent donor chimerism in patients treated with this regimen.
6. Determine the risk of acute and chronic graft-vs-host disease in patients treated with this regimen.
7. Determine the toxic effects of this regimen in these patients.
8. Determine the disease-free and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed hematologic malignancy, including one of the following:
  • Chronic lymphocytic leukemia (CLL)
    • Absolute lymphocytosis greater than 5,000/mm³
    • Lymphocytes must appear morphologically mature with less than 55% prolymphocytes
    • Lymphocyte phenotype with expression of CD19 and CD5
  • Prolymphocytic leukemia (PLL)
    • Morphologically confirmed
    • Absolute lymphocytosis greater than 5,000/mm³
    • More than 55% prolymphocytes
  • Non-Hodgkin's lymphoma or Hodgkin's lymphoma
    • Any WHO histologic subtype allowed except mantle cell lymphoma
    • Core biopsies allowed if they contain adequate tissue for primary diagnosis and immunophenotyping
    • No bone marrow biopsy as the sole diagnostic means for follicular lymphoma
  • Multiple myeloma
    • Active disease requiring treatment
    • Durie-Salmon stage I, II, or III
  • Acute myeloid leukemia
    • Documented control (i.e., less than 10% bone marrow blasts and no circulating blasts)
  • Myelodysplastic syndromes
    • Documented disease by WHO criteria



• Must have evidence of relapse/progression at least 6 months after prior high-dose chemotherapy with autologous hematopoietic stem cell support



• Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic evidence of mantle cell lymphoma



• Availability of any of the following donor types:
  • HLA-identical sibling (6/6)
  • 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci
    • Only a single mismatch at one class I or II allele allowed
  • 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B, C, DRB1, and DQB1 loci



• No syngeneic donors

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• More than 4 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior surgery

Patient Characteristics:

Age

• Under 70

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

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

Renal

• Creatinine clearance at least 40 mL/min

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 total of 20-80 patients will be accrued for this study within 10-40 months.

Outcomes

Treatment-related mortality

Complete response
Complete or mixed donor chimerism
Disease-free survival
Graft-versus-host disease

Outline

This is an open-label study.

• Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.



• Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3, and 6. Patients with a matched related or matched unrelated donor receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180 followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).

   [Note: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than 50% at day 60 or patient has progressive disease]




• Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.



• Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months for 3 years.

Bashey A, Owzar K, Johnson JL, et al.: Reduced-intensity allogeneic transplantation after failure of autologous transplantation: a prospective multi-center CALGB study. [Abstract] Blood 108 (11): A-3122, 2006.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Asad Bashey, MD, PhD, Protocol chair(Contact information may not be current)		Ph: 858-822-6600

Registry Information
Official Title		Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation
Trial Start Date		2002-12-15
Registered in ClinicalTrials.gov		NCT00053196
Date Submitted to PDQ		2002-11-15
Information Last Verified		2006-04-08
NCI Grant/Contract Number		CA31946

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