Donor Stem Cell Transplant in Treating Older or Frail Patients With Hematologic Cancer

NCT ID: NCT00296023

Last Updated: 2012-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-01-31

Study Completion Date

2008-06-30

Brief Summary

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RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and methotrexate and tacrolimus after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating older or frail patients with hematologic cancer.

Detailed Description

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OBJECTIVES:

Primary

* Determine the safety of non-myeloablative allogeneic peripheral blood stem cell transplantation, in terms of regimen-related organ toxicity and toxicity from acute graft-vs-host disease (GVHD), in older or medically frail patients with high-risk indolent hematologic malignancies.
* Determine overall survival, disease-free survival, and relapse risk at 1, 2, and 3 years post-transplantation in these patients.

Secondary

* Determine the engraftment of donor hematopoiesis at 6 weeks, 3 and 6 months, and 1 year post-transplantation in these patients.
* Determine the incidence and severity of chronic GVHD in older and medically infirm patients treated with this regimen.
* Determine the safety and efficacy of collecting peripheral blood stem cells from older donors (age \> 60 years).
* Determine the need and efficacy of donor lymphocyte infusions in patients with residual disease after transplant.

OUTLINE:

* Non-myeloablative preparative regimen:Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours every 8 hours on days -4 and -3, and anti-thymocyte globulin IV over 8 hours on days -4 to -1.
* Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 6 and continuing until blood counts recover.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus orally every 12 hours or IV continuously beginning on day -2 and continuing until day 90, followed by a taper until day 180. Patients also receive methotrexate IV over 15-30 minutes on days 1, 3, 6, and 11.
* Donor lymphocyte infusions (DLIs): Patients with residual disease ≥ 6 months post-transplantation who are off immunosuppression for ≥ 30 days with no evidence of GVHD may receive DLIs. DLIs are administered ≥ 12 weeks apart in the presence of persistent disease, absence of severe (grade 3-4) GVHD, and absence of persistent GVHD after the first DLI.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Conditions

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Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes

Keywords

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stage III chronic lymphocytic leukemia stage IV chronic lymphocytic leukemia stage III adult diffuse small cleaved cell lymphoma stage IV adult diffuse small cleaved cell lymphoma noncontiguous stage II grade 1 follicular lymphoma noncontiguous stage II grade 2 follicular lymphoma noncontiguous stage II grade 3 follicular lymphoma stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma noncontiguous stage II marginal zone lymphoma stage III marginal zone lymphoma stage IV marginal zone lymphoma noncontiguous stage II small lymphocytic lymphoma stage III small lymphocytic lymphoma stage IV small lymphocytic lymphoma noncontiguous stage II adult Burkitt lymphoma stage III adult Burkitt lymphoma stage IV adult Burkitt lymphoma stage III adult diffuse large cell lymphoma stage IV adult diffuse large cell lymphoma noncontiguous stage II adult diffuse mixed cell lymphoma stage III adult diffuse mixed cell lymphoma stage IV adult diffuse mixed cell lymphoma noncontiguous stage II adult immunoblastic large cell lymphoma stage III adult immunoblastic large cell lymphoma stage IV adult immunoblastic large cell lymphoma noncontiguous stage II adult lymphoblastic lymphoma stage III adult lymphoblastic lymphoma stage IV adult lymphoblastic lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma stage II multiple myeloma stage III multiple myeloma chronic phase chronic myelogenous leukemia primary myelofibrosis polycythemia vera prolymphocytic leukemia stage II adult Hodgkin lymphoma stage III adult Hodgkin lymphoma stage IV adult Hodgkin lymphoma de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes refractory anemia with excess blasts in transformation refractory anemia with excess blasts chronic myelomonocytic leukemia adult acute myeloid leukemia in remission secondary acute myeloid leukemia Waldenström macroglobulinemia essential thrombocythemia 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) noncontiguous stage II adult diffuse large cell lymphoma noncontiguous stage II adult diffuse small cleaved cell lymphoma stage I multiple myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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stem cell transplant

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

methotrexate

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Interventions

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anti-thymocyte globulin

Intervention Type BIOLOGICAL

filgrastim

Intervention Type BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

methotrexate

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Meets 1 of the following criteria:

* Age 60 to 75 years old AND no co-morbid illness
* Younger patients with any of the following comorbidities:

* Decreased cardiac ejection fraction
* Pulmonary dysfunction
* Elevated liver function tests
* Hepatitis C infection
* Poor performance status
* Sibling or related donor available

* Matched ≥ 5/6 HLA loci (A, B, and DR) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

* See Disease Characteristics
* ECOG performance status 0-2
* Creatinine \< 2.0 mg/dL
* Creatinine clearance \> 40 mL/min
* Ejection fraction \> 30% by echocardiogram or MUGA
* Bilirubin \< 3.0 mg/dL (if total bilirubin is elevated and Gilbert's disease is suspected, direct bilirubin must be normal)
* Alkaline phosphatase \< 4 times ULN
* AST \< 4 times ULN
* HIV negative
* Hepatitis B and/or C virus allowed if a liver biopsy (performed within the past 3 months) shows ≤ grade 2 inflammation
* No active infection

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas G. Martin, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Willis Navarro, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Charles A. Linker, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

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Alta Bates Comprehensive Cancer Center

Berkeley, California, United States

Site Status

UCSF Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Countries

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United States

Other Identifiers

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UCSF-98251

Identifier Type: -

Identifier Source: secondary_id

UCSF-9805

Identifier Type: -

Identifier Source: secondary_id

UCSF-H9996-15837-06

Identifier Type: -

Identifier Source: secondary_id

CDR0000463724

Identifier Type: -

Identifier Source: org_study_id