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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	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

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Masking:	None (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
Study Start Date :	May 2005
Actual Primary Completion Date :	November 2007

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

1. Non-relapse mortality (NRM) at 200 days

Secondary Outcome Measures :

1. Overall survival
2. Relapse rate
3. Sinusoidal obstruction syndrome (SOS)
4. Acute renal failure
5. Respiratory failure
6. Cause of death

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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Locations

United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	George B. McDonald, MD	Fred Hutchinson Cancer Research Center

More Information

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ClinicalTrials.gov Identifier:	NCT00317785 History of Changes
Other Study ID Numbers:	1998.00; FHCRC-1998.00; CDR0000471840 ( Registry Identifier: PDQ )
First Posted:	April 25, 2006
Last Update Posted:	May 7, 2010
Last Verified:	May 2010

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:

Lymphoma; Syndrome; Leukemia; Myelodysplastic Syndromes; Preleukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease; Pathologic Processes; Bone Marrow Diseases; Hematologic Diseases	Precancerous Conditions; Cyclophosphamide; Methotrexate; Tacrolimus; Cyclosporins; Cyclosporine; Sirolimus; Mycophenolic Acid; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action