Total-Body Irradiation and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer and Other Diseases

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00317785
First received: April 24, 2006
Last updated: May 5, 2010
Last verified: May 2010
  Purpose

RATIONALE: Giving total-body irradiation and chemotherapy, such as cyclophosphamide, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving total-body irradiation together with cyclophosphamide works in treating patients who are undergoing donor stem cell transplant for hematologic cancer and other diseases.


Condition Intervention Phase
Leukemia
Lymphoma
Myelodysplastic Syndromes
Drug: cyclophosphamide
Drug: cyclosporine
Drug: methotrexate
Drug: mycophenolate mofetil
Drug: sirolimus
Drug: tacrolimus
Other: pharmacological study
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Radiation: total-body irradiation
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Total Body Irradiation Plus Metabolism-Based Cyclophosphamide Dosing as Preparative Therapy for Allogeneic Hematopoietic Cell Transplant for Patients With Hematological Malignancy

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Non-relapse mortality (NRM) at 200 days [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Relapse rate [ Designated as safety issue: No ]
  • Sinusoidal obstruction syndrome (SOS) [ Designated as safety issue: No ]
  • Acute renal failure [ Designated as safety issue: No ]
  • Respiratory failure [ Designated as safety issue: No ]
  • Cause of death [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: May 2005
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the potential efficacy of targeting cyclophosphamide to a metabolic endpoint when given together with total-body irradiation, in terms of day 200 nonrelapse mortality, in patients with hematologic cancer and other diseases who are undergoing allogeneic hematopoietic stem cell transplantation.

Secondary

  • Determine the overall survival of patients treated with this regimen.
  • Determine the rate of relapse in patients treated with this regimen.
  • Determine the occurrence of sinusoidal obstruction syndrome in patients treated with this regimen.
  • Determine the occurrence of acute renal failure in these patients.
  • Determine the occurrence of respiratory failure in these patients.

OUTLINE:

  • Conditioning regimen: Patients undergo total-body irradiation twice daily on days -6 to -4. Patients also receive cyclophosphamide IV over 1 hour on day -3 and then IV at a metabolism-based dose* on day -2.

NOTE: *Patients undergo frequent blood sampling after completion of the first cyclophosphamide infusion for pharmacokinetic studies in order to determine the dose for the second cyclophosphamide infusion.

  • Allogeneic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis as per the attending physician, including one of the following regimens: cyclosporine and methotrexate; tacrolimus and methotrexate; tacrolimus and mycophenolate mofetil; or sirolimus, tacrolimus, and methotrexate (as per the GVHD prophylaxis regimen chosen for each patient).

After completion of study treatment, patients are followed periodically for at least 200 days.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of a hematologic cancer or other disease that is unlikely to respond to conventional treatment, including any of the following:

    • Chronic myelogenous leukemia
    • Acute myeloid leukemia
    • Acute lymphocytic leukemia
    • Myelodysplastic syndromes
    • Lymphoma
  • Patients who have bulky tumor mass must not require additional involved-field irradiation
  • Planning to undergo conditioning for transplantation at the Seattle Cancer Care Alliance and University of Washington Medical Center
  • Must have an HLA-matched donor available

    • No donors who are mismatched for > 1 HLA class I antigen or allele
    • Negative anti-donor lymphocytotoxic crossmatch

PATIENT CHARACTERISTICS:

  • Life expectancy must not be severely limited by diseases other than malignancy
  • No moribund patients
  • Creatinine ≤ 1.2 mg/dL
  • Oxygen saturation on room air ≥ 93%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No HIV positivity
  • No cirrhosis
  • No hepatic fibrosis with bridging
  • No fulminant hepatic failure
  • No acute liver injury
  • No persistent cholestasis
  • No infection requiring systemic antibiotic or antifungal therapy
  • No coronary artery disease
  • No congestive heart failure requiring therapy

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior hematopoietic stem cell transplantation
  • No prior radiation therapy to the liver or adjacent organs
  • More than 30 days since prior cytoreductive chemotherapy for patients with a large body burden of tumor cells
  • No concurrent enrollment in a phase I study
  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: NCT00317785

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: George B. McDonald, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00317785     History of Changes
Other Study ID Numbers: 1998.00, FHCRC-1998.00, CDR0000471840
Study First Received: April 24, 2006
Last Updated: May 5, 2010
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Fred Hutchinson Cancer Research Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
previously treated myelodysplastic syndromes
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult Burkitt lymphoma
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Leukemia
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Cyclophosphamide
Methotrexate
Mycophenolate mofetil
Mycophenolic Acid
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on October 21, 2014