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

Alternate Title

Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	0.5 to 70	NCI	JHOC-J9966 JHOC-99110501, NCI-G00-1816, NCT00006042

Objectives

1. Determine the minimum effective dose of pretransplant cyclophosphamide to induce engraftment of haploidentical allogeneic bone marrow without the use of myeloablative conditioning in patients with hematologic malignancies.
2. Determine the incidence and severity of graft versus host disease and nonhematologic toxicities with this treatment regimen in these patients.
3. Correlate the pretreatment phenotypic and functional immunologic characteristics in these patients in relation to risk of graft rejection with this treatment regimen.

Entry Criteria

Disease Characteristics:

• Patients with any of the following diagnoses:
  • Chronic myelogenous leukemia
    • Chronic phase 1
      • Failed prior interferon alfa therapy

        OR

      • Relapsed after prior autologous stem cell transplantation
    • Chronic phase 2
  • Acute leukemia
    • Standard risk
      • Age over 60 years
      • Complete remission 1 (CR1)
    • High risk
      • High WBC at presentation, unfavorable cytogenetics, mixed lineage, delayed response to induction chemotherapy
      • CR1
      • Complete remission 2 or higher
  • Acute lymphocytic leukemia
    • CR1 or higher
  • Myelodysplastic syndrome
    • Untreated

      OR

    • CR1
  • Acute myeloid leukemia in CR1
  • Chronic lymphocytic leukemia
    • Rai stage III or IV

      OR

    • Received prior autologous stem cell transplantation
  • Multiple myeloma
    • Stage II or III
    • Stable or progressive disease after prior chemotherapy

      OR

    • Received prior autologous stem cell transplantation
  • Non-Hodgkin's Lymphoma
  • Hodgkin's lymphoma



• Ineligible for or refused autologous or standard allogeneic bone marrow transplantation



• Ineligible for bone marrow transplantation from an HLA matched, sibling donor or from an HLA matched, unrelated donor



• Must have an HLA mismatched, related donor (3-5 out of 6)

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• No prior transfusions from donor

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Patient Characteristics:

Age:

• 0.5 to 70

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 3.1 mg/dL

Renal:

• Not specified

Cardiovascular:

• Left ventricular ejection fraction at least 35%

Pulmonary:

• FEV₁ and FVC at least 40% of predicted

  OR

• FEV₁ and FVC at least 60% in patients who have received prior thoracic or mantle radiotherapy

Other:

• HIV negative
• No other debilitating medical or psychiatric illness that would preclude study compliance
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

At least 23 patients will be accrued for this study.

Outline

This is a dose-escalation study of cyclophosphamide.

Patients receive fludarabine IV over 1 hour on days -6 to -2; cyclophosphamide IV over 1 hour on days -6, -5, and 3; total body irradiation on day -1; and allogeneic bone marrow transplantation on day 0. Patients also receive tacrolimus IV or orally twice a day on days 4-50; oral mycophenolate mofetil on days 4-35; and filgrastim (G-CSF) subcutaneously or IV starting on day 4 and continuing until blood counts recover.

Cohorts of 3-6 patients receive escalating doses of cyclophosphamide until the minimum effective dose necessary to induce chimerism without unacceptable toxicity in these patients is determined.

Patients are followed at 2 and 6 months, at one year, and then annually thereafter.

O'Donnell PV, Luznik L, Jones RJ, et al.: Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 8 (7): 377-86, 2002.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Ephraim J. Fuchs, MD, Protocol chair		Ph: 410-955-8143 Email: fuchsep@jhmi.edu

Registry Information
Official Title		Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide
Trial Start Date		1999-12-14
Registered in ClinicalTrials.gov		NCT00006042
Date Submitted to PDQ		2000-06-06
Information Last Verified		2004-11-18
NCI Grant/Contract Number		P30-CA06973

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