Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

NCT ID: NCT00044954

Last Updated: 2019-09-17

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

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

1999-11-30

Study Completion Date

2006-11-30

Brief Summary

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RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with donor peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining total-body irradiation with fludarabine and donor peripheral stem cell transplantation in treating patients who have hematologic cancer.

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Detailed Description

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OBJECTIVES:

* Determine the response rate and duration of response in patients with low-risk hematologic malignancies treated with low-dose total-body irradiation (TBI) and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a slow immunosuppression taper and donor leukocyte infusions (DLI).
* Determine the response rate and duration of response in patients with high-risk hematologic malignancies treated with low-dose TBI and fludarabine followed by HLA-matched allogeneic stem cell transplantation followed by a faster immunosuppression taper and DLI.
* Determine the incidence and extent of graft-versus-host disease, regimen-related toxicity, and engraftment in patients treated with these regimens.
* Assess the quality of life of patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups (high-risk vs low-risk hematologic malignancy). The high-risk group includes acute myelogenous leukemia, myelodysplastic syndromes, accelerated phase chronic myelogenous leukemia (CML), second chronic phase CML, and non-Hodgkin's lymphoma. The low-risk group includes Hodgkin's lymphoma, first chronic phase CML, multiple myeloma, and chronic lymphocytic leukemia.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total-body irradiation on day 0 followed by allogeneic stem cell transplantation. Patients also receive oral mycophenolate mofetil on days 0-28.

High-risk patients receive oral cyclosporine twice daily on days -2 to day 60. Patients with persistent disease, T-cell chimerism, and no graft-vs-host disease (GVHD) on day 90 receive up to 3 doses of donor leukocyte infusion (DLI) over the next 4 months.

Low-risk patients receive oral cyclosporine twice daily on days -2 to day 150. Patients with persistent disease, T-cell chimerism, and no GVHD on day 180 receive up to 3 doses of DLI over the next 4 months.

Quality of life is assessed at baseline and at 1, 3, 6, 9, 12, 18, and 24 months.

Patients are followed at 1, 3, 6, 9, and 12 months and then annually for 2 years.

PROJECTED ACCRUAL: A total of 120 patients (60 per group) will be accrued for this study.

Conditions

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Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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therapeutic allogeneic lymphocytes

Intervention Type BIOLOGICAL

cyclosporine

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

mycophenolate mofetil

Intervention Type DRUG

allogeneic bone marrow transplantation

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

Eligibility Criteria

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Inclusion Criteria

* Non-Hodgkin's lymphoma (NHL)

* Grade III follicular large cell (relapsed after one course of prior chemotherapy)
* Diffuse large cell (relapsed after one course of prior chemotherapy)
* Mantle cell
* Chronic lymphocytic leukemia (CLL)

* Relapsed after at least 1 course of prior therapy
* Must have 6 out of 6 HLA A-, B-, and DR- identical sibling donor

PATIENT CHARACTERISTICS:

Age

* 18 to 75 for patients with MM
* 50 to 75 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL
* 18 to 49 for patients with CML, AML, MDS, Hodgkin's lymphoma, NHL, or CLL who are considered eligible for an allogeneic bone marrow transplantation (BMT) but do not meet institutional criteria for a standard allogeneic BMT

Performance status

* Zubrod 0-2

Life expectancy

* At least 6 months

Hematopoietic

* Not specified

Hepatic

* Bilirubin no greater than 3 mg/dL

Renal

* Creatinine no greater than 2 mg/dL

Cardiovascular

* LVEF at least 40% by MUGA or echocardiogram

Pulmonary

* DLCO at least 50% of predicted

Other

* HIV negative
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No recent history of drug or alcohol abuse
* No other prior malignancy except basal cell skin cancer
* No uncontrolled bacterial, viral, fungal, or parasitic infections

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Prior autologous transplantation allowed if disease progression occurred
* No prior or concurrent tandem autologous transplantation followed by non-myeloablative-allograft protocol

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* Not specified

Radiotherapy

* Not specified

Surgery

* Not specified
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Texas Southwestern Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert H. Collins, MD

Role: STUDY_CHAIR

Simmons Cancer Center

Locations

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Rocky Mountain Cancer Centers - Denver Midtown

Denver, Colorado, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Kansas City Cancer Centers - Central

Kansas City, Missouri, United States

Site Status

Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Site Status

Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center

Nashville, Tennessee, United States

Site Status

Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Texas Transplant Institute

San Antonio, Texas, United States

Site Status

Massey Cancer Center at Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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UTSMC-0799296

Identifier Type: -

Identifier Source: secondary_id

AMGEN-UTSMC-0799296

Identifier Type: -

Identifier Source: secondary_id

IBMTR-SC-00-03.1

Identifier Type: -

Identifier Source: secondary_id

ROCHE-UTSMC-0799296

Identifier Type: -

Identifier Source: secondary_id

SPRI-UTSMC-0799296

Identifier Type: -

Identifier Source: secondary_id

NCI-V02-1705

Identifier Type: -

Identifier Source: secondary_id

CDR0000069461

Identifier Type: -

Identifier Source: org_study_id

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