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

Alternate Title

Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer or Aplastic Anemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 5 to 70 NCI RPCI-RP-0105 NCT00053989, RP 01-05

Objectives

1. Determine the safety and toxic effects of nonmyeloablative allogeneic peripheral blood stem cell transplantation in patients with a hematologic malignancy or aplastic anemia.
2. Determine clinical response and overall outcome of patients treated with this regimen.
3. Determine the incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of aplastic anemia
  • Severe disease
  • Failed at least 1 course of standard immunosuppressive regimen with cyclosporine and anti-thymocyte globulin

  OR




• Histologically confirmed hematologic malignancy including the following:
  • Acute leukemia
    • Any of the following types:
      • Acute myeloid leukemia (AML) with antecedent myelodysplastic syndromes
      • Secondary AML
      • AML with high-risk cytogenetic abnormalities
      • Acute lymphoblastic leukemia with high-risk cytogenetic abnormalities
    • Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen

      OR

    • In first remission at high risk of relapse
  • Chronic myelogenous leukemia
    • Chronic phase meeting at least 1 of the following criteria:
      • Failed imatinib mesylate
      • Failed interferon after at least 6 months of treatment with minimum of 21 million units of interferon per week
      • Unable to tolerate interferon
    • Accelerated phase (blasts less than 20%)
  • Myeloproliferative and myelodysplastic syndromes
    • Myelofibrosis (after splenectomy)
    • Refractory anemia
    • Refractory anemia with excess blasts
    • Chronic myelomonocytic leukemia
  • Lymphoproliferative disease
    • Chronic lymphocytic leukemia
      • Symptomatic disease after first-line chemotherapy
    • Low-grade non-Hodgkin's lymphoma (recurrent or persistent)
      • Symptomatic disease after first-line chemotherapy
    • Multiple myeloma
      • Progressive disease after autologous stem cell transplantation
    • Waldenstrom's macroglobulinemia
      • Failed 1 standard regimen
  • Non-Hodgkin's lymphoma meeting the following criteria:
    • Intermediate or high grade
    • Controlled and chemosensitive disease
    • First remission lymphoblastic or small non-cleaved cell lymphoma at high risk of relapse
  • Hodgkin's lymphoma
    • Relapsed and chemosensitive disease



• Not eligible for standard myeloablative allogeneic stem cell transplantation



• Availability of any of the following donor types:
  • Related donor matched at 5 or 6 HLA antigens (A, B, DR)
  • Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci
    • Single antigen mismatch at C allowed
  • Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR)

     [Note: No syngeneic donors permitted]




• No uncontrolled CNS disease (for hematologic malignancies)

 [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

• See Disease Characteristics
• At least 6 months since prior autologous bone marrow transplantation (BMT)
• At least 12 months since prior allogeneic BMT

Chemotherapy

• See Disease Characteristics
• 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

• 5 to 70 (if related donor transplantation)
• 5 to 55 (if unrelated donor transplantation)

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin less than 3 times normal
• Alkaline phosphatase less than 3 times normal
• AST/ALT less than 3 times normal
• No Child's class B or C liver failure

Renal

• Creatinine clearance greater than 40 mL/min

Cardiovascular

• Cardiac ventricular ejection fraction at least 35% by MUGA
• No cardiovascular disease

Pulmonary

• DLCO at least 40% of predicted, corrected for hemoglobin and/or alveolar ventilation

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV antibody negative
• No uncontrolled diabetes mellitus
• No active serious infection
• No other disease that would preclude study therapy
• No other concurrent malignancy except non-melanoma skin cancer
• No concurrent serious psychiatric illness

Expected Enrollment

A total of 30-60 patients will be accrued for this study within 6-7 years.

Outcomes

Safety
Toxicity
Clinical response
Overall outcome
Incidence of graft-vs-tumor effect, graft-vs-host disease, and chimerism

Outline

• Preparative regimen:
  • Matched related and unrelated donor transplantation:
    • Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine IV over 30 minutes on days -5 to -1.
  • Cord blood transplantation:
    • Patients receive the same regimen as above plus anti-thymocyte globulin IV over 4 hours on days -3 to -1.



• Graft-vs-host disease (GVHD) prophylaxis:
  • Matched related and unrelated donor transplantation:
    • Patients receive oral tacrolimus (or IV) once daily and oral mycophenolate mofetil (MMF) (or IV) twice daily on days -1 to 60 followed by tapering* of this regimen. Patients then receive methotrexate IV on days 1, 3, and 6.

       [Note: *This regimen is tapered from days 30-60 if donor chimerism of T-cells is 100%. MMF is then stopped and tacrolimus is tapered by 25% every 10 days and discontinued by day 90 if no GVHD develops.]

  • Cord blood transplantation:
    • Patients receive tacrolimus and MMF in the same regimen as above plus methylprednisolone twice daily on days 1-19 or until blood counts recover.



• Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.



• Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.

Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 3 years.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Philip McCarthy, MD, Protocol chair		Ph: 716-845-8412 Email: philip.mccarthy@roswellpark.org

U.S.A.
New York
	Buffalo
	Roswell Park Cancer Institute
		Clinical Trials Office - Roswell Park Cancer Institute	Ph:  877-275-7724

Registry Information
Official Title		Non-Myeloablative Allogeneic Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies and Aplastic Anemia
Trial Start Date		2001-12-07
Trial Completion Date		2010-10-18 (estimated)
Registered in ClinicalTrials.gov		NCT00053989
Date Submitted to PDQ		2002-12-13
Information Last Verified		2008-08-28
NCI Grant/Contract Number		CA16056