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

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00317785

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 Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Procedure: pharmacological study Procedure: total-body irradiation	Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma

Drug Information available for: Cyclophosphamide Methotrexate Tacrolimus Cyclosporin Cyclosporine Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Sirolimus Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

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:	October 2008 (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

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

National Cancer Institute (NCI)

Investigators

Principal Investigator:

George B. McDonald, MD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000471840, FHCRC-1998.00
Study First Received:	April 24, 2006
Last Updated:	January 13, 2009
ClinicalTrials.gov Identifier:	NCT00317785
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Blast Crisis
Sezary syndrome
Cyclosporine
Chronic myelogenous leukemia
Miconazole
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Cyclosporins
Lymphoma, large-cell, immunoblastic
Mycoses
Preleukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil

Neoplasm Metastasis
Methotrexate
Acute myeloid leukemia, adult
Hodgkin Disease
Myelodysplastic syndromes
Chronic lymphocytic leukemia
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Acute myelogenous leukemia
Leukemia, Myeloid
Folic Acid
Leukemia, Myeloid, Accelerated Phase

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Antifungal Agents
Abortifacient Agents
Alkylating Agents

Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 16, 2009