Radiation Therapy and Fludarabine Followed by Donor Peripheral Stem Cell Transplantation, Mycophenolate Mofetil, and Cyclosporine in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00014235

Purpose

RATIONALE: Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells from a donor can be rejected by the body's normal cells. Mycophenolate mofetil and cyclosporine may prevent this from happening.

PURPOSE: Phase I/II trial to study the effectiveness of radiation therapy and fludarabine followed by donor peripheral stem cell transplantation, mycophenolate mofetil, and cyclosporine in treating patients who have hematologic cancer.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: therapeutic allogeneic lymphocytes Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Nonmyeloablative PBSC Allografting From HLA Matched Related Donors Using Fludarabine And Low Dose TBI With Disease-Risk Based Immunosuppression

Resource links provided by NLM:

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

Study Start Date:

December 2000

Detailed Description:

OBJECTIVES:

Determine the rate of grade III/IV graft-versus-host disease (GVHD) in patients with hematologic malignancies treated with low-dose radiotherapy and fludarabine followed by allogeneic peripheral blood stem cell transplantation, mycophenolate mofetil, and cyclosporine.
Determine the risk of graft rejection and GVHD in patients treated with this regimen.
Determine the non-relapse mortality and disease response in patients treated with this regimen.
Determine the incidence and severity of infectious complications in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are assigned to one of two treatment regimens according to disease risk (indolent vs aggressive).

Patients may receive cytoreductive chemotherapy and/or radiotherapy to high-risk sites of bulky disease. All patients then receive conditioning therapy comprising fludarabine IV on days -4 to -2. Patients undergo low-dose total body irradiation followed by unmodified allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients receive oral mycophenolate mofetil (MMF) daily on days 0-27.

Regimen A

Indolent disease including:
- Chronic lymphocytic leukemia, chronic myelogenous leukemia (CML) in first chronic phase
- Acute myeloid leukemia (AML) in first complete remission (CR)
- Refractory anemia with ringed sideroblasts (RARS)
- Myeloma in CR or partial remission (PR)
- Low-grade non-Hodgkin's lymphoma (NHL)
- Aggressive NHL in first CR Patients receive oral cyclosporine twice daily beginning on day -3. If there is no evidence of graft-versus-host disease (GVHD), cyclosporine is tapered from day 56 until discontinuation by day 180. Beginning at least 2 weeks after completion of cyclosporine, patients with progressive disease receive donor lymphocyte infusion (DLI) IV over 30 minutes for up to 3 infusions. Patients with stable disease may receive DLI at 9-12 months post-transplantation.

Regimen B

Aggressive disease including:
- CML in accelerated phase or greater than first CR
- AML beyond first CR
- Myelodysplastic syndrome other than RARS
- Myeloma not in CR/PR
- Other NHL Patients receive oral cyclosporine twice daily beginning on day -3. If there is no evidence of GVHD, cyclosporine is tapered from day 56 until discontinuation by day 77. Beginning at least 2 weeks after the completion of cyclosporine, patients with persistent disease receive DLI IV over 30 minutes for up to 3 infusions.

Patients are followed at day 84, months 4, 6, 12, 18, and 24, and then annually thereafter.

PROJECTED ACCRUAL: A total of 160 patients (80 per risk group) will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	up to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Over 49 and under 75 years of age with diagnosis of non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma
- Ineligible for curative autologous peripheral blood stem cell (PBSC) or bone marrow transplantation (BMT) OR
- Failed prior autologous PBSC or BMT
- NHL and CLL patients:
  - Failed prior therapy with an alkylating agent and/or fludarabine OR
  - At high risk of relapse
- Multiple myeloma patients:
  - Stage II or III disease
  - Prior chemotherapy required OR
Under 50 years of age with diagnosis of NHL, Hodgkin's lymphoma, CLL, or multiple myeloma
- High risk of regimen-related toxicity due to prior autologous PBSC or BMT or pre-existing medical conditions OR
Under 75 years of age with diagnosis of other malignant disease amenable to treatment with allogeneic BMT
- High risk for regimen-related toxicity with standard high-dose regimens due to pre-existing chronic disease of the kidneys, liver, lungs, or heart
- Including, but not limited to, the following diseases:
  - Myelodysplastic syndromes
  - Myeloproliferative syndromes
  - Acute leukemia with less than 10% blasts in bone marrow
  - Amyloidosis
  - Hodgkin's lymphoma
Ineligible for high-priority curative autologous PBSC or BMT
No rapidly progressive aggressive NHL unless in minimal disease state
No CNS involvement
Must have genotypically or phenotypically HLA identical related donor that meets all of the following criteria:
- 12 to 74 years of age
- Not an identical twin
- Not pregnant
- HIV negative
- No know allergy to filgrastim (G-CSF)
- No concurrent serious systemic illness

PATIENT CHARACTERISTICS:

Age:

Under 75

Performance status:

Karnofsky 50-100%

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 2 times upper limit of normal (ULN)
SGPT and SGOT no greater than 4 times ULN

Renal:

Renal failure allowed
Creatinine no greater than 2.0 mg/dL

Cardiovascular:

No poorly controlled hypertension (blood pressure 150/90 or greater while receiving standard medication)
Ejection fraction at least 40%

Pulmonary:

No supplementary continuous oxygen
DLCO at least 30%
Total lung capacity (TLC) at least 30%
FEV_1 at least 30%

Other:

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

PRIOR CONCURRENT THERAPY:

Biologic therapy:

See Disease Characteristics
No concurrent growth factors on days 0-27

Chemotherapy:

See Disease Characteristics

Endocrine therapy:

Not specified

Radiotherapy:

Not specified

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00014235

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Stanford University Medical Center
Stanford, California, United States, 94305-5623
Stanford University
Stanford, California, United States, 94305
United States, Colorado
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, United States, 80010
United States, Oregon
Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
United States, Wisconsin
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, United States, 53226
Germany
Universitaet Leipzig
Leipzig, Germany, D-04103
Italy
University of Torino
Torino, Italy, 10126

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

David G. Maloney, MD, PhD

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:	CDR0000068521, FHCRC-1596.00, NCI-H01-0068
Study First Received:	April 10, 2001
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00014235 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
refractory chronic lymphocytic leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia

untreated childhood acute myeloid leukemia and other myeloid malignancies
untreated childhood acute lymphoblastic 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
chronic idiopathic myelofibrosis
childhood acute promyelocytic leukemia (M3)
recurrent/refractory childhood Hodgkin lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma

Additional relevant MeSH terms:

Anti-Infective Agents
Cyclosporine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Mycophenolic Acid
Cyclosporins
Preleukemia
Hemorrhagic Disorders
Pathologic Processes
Therapeutic Uses
Mycophenolate mofetil
Cardiovascular Diseases
Dermatologic Agents
Immunoproliferative Disorders

Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Multiple Myeloma
Neoplasms
Fludarabine
Lymphoma, Non-Hodgkin
Antimetabolites
Vidarabine
Precancerous Conditions
Immunologic Factors
Blood Protein Disorders
Antineoplastic Agents
Paraproteinemias
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on November 30, 2009