Low-Dose Fludarabine, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

NCT ID: NCT00301951

Last Updated: 2017-10-12

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

PHASE1

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-09-30

Study Completion Date

2009-07-31

Brief Summary

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RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant helps stop both the growth of cancer cells and the patient's immune system from rejecting the donor's stem 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 chemotherapy, such as fludarabine and busulfan, and antithymocyte globulin before transplant and tacrolimus and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving low-dose fludarabine and busulfan together with anti-thymocyte globulin, followed by donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.

Detailed Description

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OBJECTIVES:

Primary

* Assess the feasibility of performing umbilical cord blood transplants in older patients or younger infirm patients with advanced hematologic malignancies using a reduced-intensity preparative regimen, as determined by \> 80% engraftment rate at day 180 and a \< 50% transplant-related mortality rate at day 100.

Secondary

* Describe the time to neutrophil and platelet recovery in patients treated with this regimen.
* Determine disease-specific, event-free, and overall survival rate at days 180 and 360.
* Determine the incidence, severity, and timing of acute and chronic graft-versus-host disease in patients treated with this regimen.
* Evaluate T-cell, B-cell, and natural killer cell recovery in patients treated with this regimen.
* Assess lineage-specific chimerism after transplantation and describe the contribution of each individual cord blood unit to post-transplantation hematopoiesis.

OUTLINE: This is a pilot study.

* Reduced-intensity preparative regimen: Patients receive fludarabine IV over 30 minutes on days -8 to -4, busulfan IV over 2 hours 4 times daily on days -4 and -3, and anti-thymocyte globulin IV over 6 hours on days -3 to -1.
* Allogeneic umbilical cord blood transplantation: Patients undergo allogeneic umbilical cord blood transplant on day 0. Patients receive sargramostim (GM-CSF) subcutaneously or IV beginning on day 7 and continuing until blood counts recover.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally (as tolerated) beginning on day -2 and continuing for approximately 9 months. Patients also receive oral mycophenolate mofetil twice daily on days 1-50.

After completion of study treatment, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Conditions

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Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes

Keywords

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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 angioimmunoblastic T-cell lymphoma blastic phase chronic myelogenous leukemia chronic myelomonocytic leukemia chronic phase chronic myelogenous leukemia de novo myelodysplastic syndromes extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue anaplastic large cell lymphoma nodal marginal zone B-cell lymphoma previously treated myelodysplastic syndromes recurrent adult acute lymphoblastic leukemia recurrent adult acute myeloid leukemia recurrent adult T-cell leukemia/lymphoma recurrent adult Hodgkin lymphoma recurrent adult diffuse large cell lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent mycosis fungoides/Sezary syndrome recurrent small lymphocytic lymphoma refractory chronic lymphocytic leukemia stage III adult T-cell leukemia/lymphoma refractory multiple myeloma relapsing chronic myelogenous leukemia secondary acute myeloid leukemia secondary myelodysplastic syndromes splenic marginal zone lymphoma stage I multiple myeloma stage II multiple myeloma stage IV adult T-cell leukemia/lymphoma stage III adult Hodgkin lymphoma stage III adult diffuse large cell lymphoma stage III chronic lymphocytic leukemia stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage III mantle cell lymphoma stage III marginal zone lymphoma stage III multiple myeloma stage III small lymphocytic lymphoma stage IV adult Hodgkin lymphoma stage IV adult diffuse large cell lymphoma stage IV chronic lymphocytic leukemia stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma stage IV mantle cell lymphoma stage IV marginal zone lymphoma stage IV small lymphocytic lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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cord blood transplant

Group Type EXPERIMENTAL

anti-thymocyte globulin

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

umbilical cord blood transplantation

Intervention Type PROCEDURE

Interventions

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anti-thymocyte globulin

Intervention Type BIOLOGICAL

sargramostim

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

umbilical cord blood transplantation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Diffuse large cell
* Follicular large cell
* Mantle cell
* Peripheral T-cell
* T-natural killer (T-NK) cell
* Hodgkin's lymphoma
* Must have progressed, recurred after prior therapy, or failed to respond to primary therapy
* Relapsed disease after autologous stem cell transplantation (SCT) allowed
* Low-grade non-Hodgkin's lymphoma meeting 1 of the following criteria:

* Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
* Relapsed after autologous SCT
* Chronic lymphocytic leukemia

* Relapsed or refractory disease after ≥ 2 chemotherapy-based treatment regimens
* Relapsed after autologous SCT
* Meets 1 of the following criteria:

* Age 55-70 years
* Under age 55 and deemed ineligible for conventional high-dose chemotherapy, as indicated by any of the following:

* Poor cardiac function (i.e., LVEF \< 40%)
* Poor pulmonary function (i.e., DLCO \< 50%)
* Hepatic dysfunction
* Prior myeloablative therapy
* Not eligible for autologous SCT or conventional therapy
* Umbilical cord blood donor available

* Matched at ≥ 4 of 6 HLA antigens (A, B, and DR)
* Has 1-3 units of umbilical cord blood available
* Must not have an HLA-identical or 1 antigen mismatched related donor or potential HLA-matched unrelated donor readily available 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:

* ECOG performance status 0-2
* Creatinine clearance \> 40 mL/min
* Creatinine \< 2.0 mg/dL
* AST and alkaline phosphatase \< 3 times upper limit of normal (ULN)
* Bilirubin \< 2.0 mg/dL
* Hepatitis C or active hepatitis B virus (HBV) allowed if ≤ grade 2 fibrosis and/or inflammation by liver biopsy

* Patients with history of HBV infection should be tested for hepatitis B epsilon (HBe) antigen, anti-HBe, and HBV DNA (quantitative)
* Patients with active HBV viral replication should receive antiviral therapy
* Ejection fraction \> 30%
* DLCO ≥ 40%
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active infection requiring ongoing antibiotic treatment
* HIV negative

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 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

Locations

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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-04253

Identifier Type: -

Identifier Source: secondary_id

UCSF-2407

Identifier Type: -

Identifier Source: secondary_id

UCSF-H24045-25271-02

Identifier Type: -

Identifier Source: secondary_id

CDR0000465362

Identifier Type: -

Identifier Source: org_study_id