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

Not Applicable

Completed

• Conditions: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
• Interventions: Biological: anti-thymocyte globulin; Biological: filgrastim; Biological: therapeutic allogeneic lymphocytes; Drug: busulfan; Drug: fludarabine phosphate; Drug: methotrexate; Drug: tacrolimus; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

• Registration Number: NCT00296023
• Lead Sponsor: University of California, San Francisco

Brief Summary

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

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.

Study Timeline

• Study Start: 1999-01
• Study First Submitted: 2006-02-23
• Study First Submitted QC: 2006-02-23
• Study First Posted: 2006-02-24
• Primary Completion: 2007-06
• Study Completion: 2008-06
• Status Verified: 2012-10
• Last Update Submitted: 2012-10-02
• Last Update Posted: 2012-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
stem cell transplant	therapeutic allogeneic lymphocytes	-
stem cell transplant	anti-thymocyte globulin	-
stem cell transplant	filgrastim	-
stem cell transplant	busulfan	-
stem cell transplant	tacrolimus	-
stem cell transplant	nonmyeloablative allogeneic hematopoietic stem cell transplantation	-
stem cell transplant	peripheral blood stem cell transplantation	-
stem cell transplant	fludarabine phosphate	-
stem cell transplant	methotrexate	-

Primary Outcome Measures

Name	Time	Method
Toxicity and survival	up to 36 months post transplant

Trial Locations

Locations (2)

Alta Bates Comprehensive Cancer Center; 🇺🇸 Berkeley, California, United States

UCSF Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States