Chemotherapy, Low-Dose Total-Body Irradiation, and Peripheral Stem Cell Transplantation Followed By Chemotherapy and Donor Lymphocyte Infusion in Treating Older Patients With Chronic Myeloid Leukemia - 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:	NCT00003145

Purpose

RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy and radiation therapy used to kill cancer cells. Sometimes the transplanted cells can be rejected by the body's tissues. Cyclosporine, mycophenolate mofetil, and donor lymphocytes may prevent this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine and low-dose total-body irradiation together with allogeneic stem cell transplantation works in treating older patients with chronic myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Induction of Mixed Hematopoietic Chimerism Using Fludarabine, Low-Dose TBI, PBSC Infusion and Post-Transplantation Immunosuppression With Cyclosporine and Mycophenolate Mofetil To Be Folllowed By Donor Lymphocyte Infusion in Older Patients With Chronic Myeloid Leukemia in Chronic and Accelerated Phases: A Multicenter Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

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

Primary Outcome Measures:

Efficacy and safety of establishing mixed chimerism using a non-lethal conditioning regimen [ Designated as safety issue: Yes ]
Success and safety of converting mixed chimerism to full donor chimerism using donor lymphocyte infusions [ Designated as safety issue: Yes ]

Estimated Enrollment:	20
Study Start Date:	November 1997

Detailed Description:

OBJECTIVES:

Determine whether mixed hematopoietic chimerism can be safely established with fludarabine, low-dose total body irradiation, and allogeneic peripheral blood stem cell transplantation followed by immunosuppression with cyclosporine and mycophenolate mofetil and donor lymphocyte infusion in older patients with chronic or accelerated phase chronic myelogenous leukemia.
Determine whether mixed chimerism can be converted to full donor hematopoietic chimerism with infusions of donor lymphocytes in these patients.

OUTLINE: This is a pilot, multicenter study.

Patients receive fludarabine IV on days -4 to -2 and low-dose total body irradiation followed by allogeneic peripheral blood stem cell transplantation on day 0. Patients receive oral cyclosporine twice daily on days -3 to 56 followed by a taper. Patients also receive oral mycophenolate mofetil twice daily on days 0-27.

At least 2 weeks after completion of cyclosporine and mycophenolate mofetil, patients with persistent or progressive disease receive donor lymphocytes IV over 30 minutes. In the absence of active graft-versus-host disease, patients may receive a total of 3 donor lymphocyte infusions at increasing cell doses.

Patients are followed weekly until 90 days after the last donor cell infusion, monthly for 6 months, every 6 months for 2 years, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	66 Years to 74 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed chronic myelogenous leukemia in first or second chronic or first accelerated phase
Philadelphia chromosome positive
Must have an HLA genotypically identical related donor (excluding identical twins)
Not in interferon-induced complete or partial cytogenetic remission
May be 65 years of age and under only if at high risk of regimen-related toxicity due to pre-existing chronic disease affecting liver, lungs, and heart OR at the discretion of the principal investigator

PATIENT CHARACTERISTICS:

Age:

See Disease Characteristics
66 to 74

Performance status:

Karnofsky 70-100% (Karnofsky 50-100% for patients age 65 and under)

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

See Disease Characteristics
Bilirubin no greater than 2 times upper limit of normal (ULN)*
SGOT and SGPT no greater than 2 times ULN (4 times ULN for patients age 65 and under)* NOTE: * Unless due to malignancy

Renal:

Renal failure allowed

Cardiovascular:

See Disease Characteristics
No poorly controlled hypertension
Ejection fraction at least 40% (for patients with a history of cardiac disease or anthracycline use)
No history of congestive heart failure (for patients age 65 and under)

Pulmonary:

See Disease Characteristics
DLCO at least 50% of predicted
No severe defects in pulmonary function testing*
No supplementary continuous oxygen* NOTE: * For patients age 65 and under

Other:

HIV negative
Not pregnant
Fertile patients must use effective contraception during and for 12 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
At least 1 month since prior interferon alfa

Chemotherapy:

Not specified

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003145

Locations

United States, California
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305-5623
United States, Texas
Texas Oncology, P.A. at Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, Italy, 10126

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Brenda Sandmaier, MD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000065928, FHCRC-1209.00, NCI-G97-1359
Study First Received:	November 1, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00003145 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Study placed in the following topic categories:

Antimetabolites
Philadelphia Chromosome
Cyclosporine
Immunologic Factors
Hematologic Diseases
Mycophenolic Acid
Myeloproliferative Disorders
Leukemia, Myeloid
Leukemia, Myeloid, Chronic-Phase
Fludarabine monophosphate
Immunosuppressive Agents

Cyclosporins
Anti-Bacterial Agents
Leukemia
Leukemia, Myeloid, Accelerated Phase
Antifungal Agents
Mycophenolate mofetil
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Chronic Myelogenous Leukemia
Fludarabine
Antirheumatic Agents
Bone Marrow Diseases

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Antibiotics, Antineoplastic
Cyclosporins
Leukemia
Antifungal Agents
Therapeutic Uses
Mycophenolate mofetil

Dermatologic Agents
Neoplasms by Histologic Type
Hematologic Diseases
Myeloproliferative Disorders
Enzyme Inhibitors
Fludarabine monophosphate
Leukemia, Myeloid
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Fludarabine
Bone Marrow Diseases
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 02, 2009