Cyclophosphamide Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00006042
First received: July 5, 2000
Last updated: March 9, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: filgrastim
Drug: cyclophosphamide
Drug: fludarabine phosphate
Drug: mycophenolate mofetil
Drug: tacrolimus
Procedure: allogeneic bone marrow transplantation
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Non-Myeloablative Allogeneic Bone Marrow Transplantation for Hematologic Malignancies Using Haploidentical Donors: A Phase I Trial of Pre-Transplant Cyclophosphamide

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Study Start Date: December 1999
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.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006042

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Ephraim J. Fuchs, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00006042     History of Changes
Other Study ID Numbers: CDR0000068057, J9966, P30CA006973, JHOC-J9966, JHOC-99110501, NCI-G00-1816
Study First Received: July 5, 2000
Last Updated: March 9, 2010
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent adult Hodgkin lymphoma
Burkitt lymphoma
refractory multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
chronic phase chronic myelogenous leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
recurrent/refractory childhood Hodgkin lymphoma
stage II adult lymphoblastic lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasms, Plasma Cell
Plasmacytoma
Preleukemia
Syndrome
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Disease
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Pathologic Processes
Precancerous Conditions
Vascular Diseases
Cyclophosphamide
Fludarabine
Fludarabine phosphate

ClinicalTrials.gov processed this record on October 29, 2014