Donor Stem Cell Transplant Followed By Donor White Blood Cell Infusions in Treating Young Patients With Hematologic Cancer

NCT ID: NCT00301860

Last Updated: 2013-07-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-01-31
• Study Completion Date: 2007-11-30

Brief Summary

RATIONALE: Giving chemotherapy before a donor peripheral blood stem cell 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 melphalan, and antithymocyte globulin before transplant and cyclosporine and methotrexate after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well donor stem cell transplant, using low-dose chemotherapy and antithymocyte globulin, followed by donor white blood cell infusions work in treating young patients with hematologic cancer.

Detailed Description

OBJECTIVES:

• Determine the feasibility of allogeneic hematopoietic stem cell transplantation using a reduced-intensity conditioning regimen, in terms of whole blood engraftment rate at 100 days post transplant, in pediatric patients with hematopoietic malignancies who are at high risk for complications with conventional transplantation.
• Determine the feasibility of donor lymphocyte infusions (DLIs), in terms of number of patients who receive at least one DLI by 12 months post transplant, in patients treated with this regimen.
• Determine the toxicities of the conditioning regimen, in terms of 100-day post transplant nonrelapse-related death rate, in these patients.
• Determine the toxicity of DLI, in terms of acute and chronic graft-vs-host disease rate and 12-month post transplant nonrelapse-related death rate, in these patients.

OUTLINE: This is a pilot study.

• Reduced-intensity conditioning regimen: Patients receive fludarabine IV on days -6 to -2; antithymocyte globulin IV on days -5 to -2; and melphalan IV on days -3 and -2.
• Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients also receive filgrastim (G-CSF) IV beginning on day 5 and continuing until blood counts recover.
• Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally beginning on day -1 and continuing until at least day 28 and methotrexate IV on days 1, 3, and 6.
• Donor lymphocyte infusion (DLI): Patients with mixed chimerism, no acute GVHD requiring therapy, and no relapse/progression post transplant at day 90 may receive DLI. At least 30 days after discontinuation of immunosuppression, patients may receive up to 2 DLIs at least 8-12 weeks apart in the absence of GVHD.

At the 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

Leukemia; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

cyclosporine

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Exclusion Criteria

• Shortening fraction < 30%
• History of disseminated fungal infection during chemotherapy OR currently receiving antifungal agents OR history of ≥ 2 septic episodes (confirmed by cultures) that required ICU support

• Patients with improving fungal or other infections eligible

• Improving infection is defined as confirmed negative cultures on 2 separate occasions, at least 1 week apart, and/or stable or improving imaging studies (e.g., CT scan) of the infected site
• Two imaging studies taken at least 2 weeks apart must show stable or improved disease
• History of stroke or abnormal MRI/MRA OR leukoencephalopathy OR seizures that are not fully controlled with anticonvulsants (> 2 episodes of seizures in the preceding year or 1 episode of status epilepticus in a patient who is receiving anticonvulsant therapy)
• History of prior significant bleeding (e.g., pulmonary, CNS, or gastrointestinal) OR history of a clotting disorder as manifested by prior significant thromboses (e.g., superior vena cava, inferior vena cava, or femoral vein)
• Failed conventional therapies and not eligible for myeloablative protocols

• May have failed prior conventional HSCT
• No active CNS leukemia
• Unrelated or related donor available, meeting the following criteria:

• Matched for at least 7/8 loci by high-resolution typing
• One mismatch at A, B, or C loci allowed
• Fully matched at DRB1 locus

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• No active/progressing viral, bacterial, protozoal, or fungal infection
• Transaminases ≤ 5 times normal (except in the presence of autoimmune liver disease)
• Shortening fraction ≥ 25%
• DLCO ≥ 40% OR pulse oximetry ≥ 85% on room air
• Glomerular filtration rate ≥ 40 mL/min

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior prolonged intensive chemotherapy (> 3 years of therapy or ≥ 3 different chemotherapeutic protocols) allowed

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Biljana Horn, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Countries

United States

Other Identifiers

UCSF-02164

Identifier Type: -

Identifier Source: secondary_id

UCSF-H10216-21819-03

Identifier Type: -

Identifier Source: secondary_id

CDR0000462439

Identifier Type: -

Identifier Source: org_study_id