Donor Stem Cell Transplant in Treating Patients With High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

NCT ID: NCT01027000

Last Updated: 2023-05-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-28

Study Completion Date

2023-04-30

Brief Summary

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RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Also, monoclonal antibodies, such as rituximab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus, sirolimus, and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with high-risk chronic lymphocytic leukemia or small lymphocytic lymphoma.

Detailed Description

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OBJECTIVES:

Primary

* To determine if this treatment can improve 2-year current progression-free survival (PFS) in the early disease cohort compared to historical controls. Specifically, we plan to study whether we can achieve 2-year PFS ≥ 70% and to exclude 2 year PFS ≤ 50%

Secondary

* To determine whether in the advanced disease cohort we can achieve 2-year current PFS ≥ 50% and to exclude 2-year PFS ≤ 30%
* To assess objective response rate.
* To assess the incidence of grade 2-4 and 3-4 acute graft-vs-host disease (GVHD).
* To assess the incidence of extensive chronic GVHD.
* To assess the incidence of treatment-related mortality at 100 days and 1 year
* To assess overall survival
* To assess donor chimerism for CD3+ cells at 1 and 2 years after transplantation
* To investigate the presence of donor antigen-specific T-cell clones before and after withdrawal of immune suppression.
* To compare the relapse profiles of patients with T-cell responses against CLL to those whose CLL cells are not reactive
* To prospectively examine the impact of high-risk genomic features and immune-based single nucleotide polymorphisms on response, toxicity, and 2-year PFS to reduced intensity allogeneic stem cell transplant

OUTLINE: This is a multicenter study.

* Preparative regimen: Patients receive 1 of 2 preparative regimens at the discretion of the participating institution.

* Preparative regimen 1: Patients receive rituximab IV on days -7, -1, 7, and 14 and fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -5 to -2. .
* Preparative regimen 2: Patients receive rituximab IV on days -7, -1, 7, and 14, fludarabine phosphate IV over 30 minutes on days -5 to -2, and cyclophosphamide IV over 1-2 hours on days -5 to -3. Patients with matched unrelated donors also receive anti-thymocyte globulin IV over 4-6 hours on days -6 to -4.
* Graft-vs-host disease (GVHD) prophylaxis: Patients who receive preparative regimen 1 may receive either GVHD prophylaxis regimen 1 or 2; patients who receive preparative regimen 2 may only receive GVHD prophylaxis regimen 2.

* GVHD prophylaxis regimen 1: Patients receive tacrolimus either orally or IV and oral sirolimus beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6.
* GVHD prophylaxis regimen 2: Patients receive tacrolimus either orally or IV beginning on day -2 and continuing until day 60, followed by a taper until day 180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
* Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0.
* Maintenance therapy: Patients receive rituximab IV at 3, 6, 9, and 12 months after transplantation.

Peripheral blood and bone marrow aspirate samples may be collected periodically for correlative laboratory studies.

Patients are followed up periodically for a maximum of 5 years from study entry.

Conditions

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Leukemia 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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Treatment (Combination of chemotherapy and transplant)

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Group Type EXPERIMENTAL

rituximab

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

methotrexate

Intervention Type DRUG

sirolimus

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

allogeneic stem cell transplant

Intervention Type PROCEDURE

Interventions

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rituximab

Intervention Type BIOLOGICAL

busulfan

Intervention Type DRUG

cyclophosphamide

Intervention Type DRUG

fludarabine phosphate

Intervention Type DRUG

methotrexate

Intervention Type DRUG

sirolimus

Intervention Type DRUG

tacrolimus

Intervention Type DRUG

allogeneic stem cell transplant

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

4. Donors must be healthy and must be an acceptable donor as per institutional standards for stem cell donation.
5. There will be no donor age restriction.
Minimum Eligible Age

18 Years

Maximum Eligible Age

69 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Biologics, Inc.

INDUSTRY

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Edwin P. Alyea, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

Site Status

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Site Status

Union Hospital of Cecil County

Elkton, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana-Farber/Brigham and Women's Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Site Status

Long Island Jewish Medical Center

New Hyde Park, New York, United States

Site Status

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Countries

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United States

Other Identifiers

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CDR0000660555

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01995

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB 100701

Identifier Type: -

Identifier Source: org_study_id

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