Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

March 9, 2010 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells.

PURPOSE: Phase I trial to study the effectiveness of cyclophosphamide plus bone marrow transplantation in treating patients who have hematologic cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • 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.
  • Determine the incidence and severity of graft versus host disease and nonhematologic toxicities with this treatment regimen in these patients.
  • Correlate the pretreatment phenotypic and functional immunologic characteristics in these patients in relation to risk of graft rejection with this treatment regimen.

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.

PROJECTED ACCRUAL: At least 23 patients will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

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:

  • FEV_1 and FVC at least 40% of predicted OR
  • FEV_1 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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Ephraim J. Fuchs, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 1999

Study Registration Dates

First Submitted

July 5, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

March 10, 2010

Last Update Submitted That Met QC Criteria

March 9, 2010

Last Verified

March 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000068057, J9966
  • P30CA006973 (U.S. NIH Grant/Contract)
  • JHOC-J9966
  • JHOC-99110501
  • NCI-G00-1816

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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