Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

Official Title: “Pentostatin and Donor Lymphocyte Infusion for Low Donor T-Cell Chimerism After Hematopoietic Cell Transplantation Using Nonmyeloablative Conditioning - A Multicenter Trial”

This clinical trial studies pentostatin and donor lymphocyte infusion in preventing graft rejection in patients who have undergone donor stem cell transplant. Giving pentostatin and an infusion of the donor's T cells (donor lymphocyte infusion) after a donor stem cell transplant may stop the patient's immune system from rejecting the donor's stem 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 pentostatin before donor lymphocyte infusion may stop this from happening

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of the combined use of pentostatin and donor lymphocyte infusion (DLI) in patients with low or falling donor T-cell chimerism to prevent graft rejection after nonmyeloablative marrow transplantation both from matched related donors (MRDs) or unrelated donors (URDs).

SECONDARY OBJECTIVES:

I. To determine the incidence of graft-versus-host disease (GvHD) infections, and disease response (if persistent disease is present).

OUTLINE: This is a dose-escalation study of donor lymphocyte infusion. Patients are assigned to 1 of 2 treatment groups.

GROUP I: Patients receive pentostatin intravenously (IV) over 20-30 minutes on day -2 and DLI over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same cluster of differentiation (CD)3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart.

GROUP II (initiated if patients in group I do not achieve sustained engraftment and improved chimerism): Patients receive treatment as in group I. Patients also receive oral cyclosporine twice daily on days -3 to 56 and oral mycophenolate mofetil once daily on days 0 to 27. Treatment continues in the absence of GvHD.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually thereafter.

Intervention(s) in this Clinical Trial

• Drug: pentostatin
  • Given IV
• Biological: therapeutic allogeneic lymphocytes
  • Given IV
• Drug: mycophenolate mofetil
  • Given orally
• Drug: cyclosporine
  • Given orally

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Treatment (
  • See Detailed Description

Primary Measures

• Safety of the combined use of pentostatin and DLI as defined by an acceptable rate of grade IV acute GVHD
  • Time Frame: Within 100 days after the last DLI
    Safety Issue?: Yes
• Efficacy of the combined use of pentostatin and DLI defined as an increase of at least 10 percentage points in donor T-cell chimerism
  • Time Frame: From the time of enrollment maintained to day 56 after the last DLI
    Safety Issue?: No

Secondary Measures

• Incidence of grade II-IV acute GVHD infection
  • Time Frame: Day 84 and 1 year
    Safety Issue?: No
• Incidence of chronic GVHD infection
  • Time Frame: Day 84 and 1 year
    Safety Issue?: No
• Disease response of the combined use of pentostatin and DLI
  • Time Frame: Every 6 months for 2 years and then annually thereafter
    Safety Issue?: No

Inclusion Criteria:

• Only patients having received a preceding nonmyeloablative allogeneic transplantation with fludarabine/2-3 Gy total-body irradiation (TBI) or 2 Gy TBI conditioning from either a related or unrelated donor are eligible for this protocol
• Patients with less than 50% donor CD3 peripheral blood chimerism on two separate, consecutive evaluations (the two evaluations must be at least 14 days apart) OR patients with absolute decreases of donor CD3 peripheral blood chimerism of >= 20% if the second test shows < 50% donor CD3 cells (the two evaluations must be at least 14 days apart)
• Patients with evidence of disease are only eligible if the disease is stable (or persistent) in comparison to the status prior to transplantation
• Patients must be tapered off systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day; additionally, all other immunosuppressive therapy will be discontinued before administration of pentostatin
• Patients must have persistent donor CD3 cells (>= 5% donor CD3 cells by a deoxyribonucleic acid (DNA)-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number of tandem repeats (VNTR)])
• DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the following criteria apply for the DLI product:
• DONOR: Original donor of hematopoietic cell transplantation
• DONOR: Donor must give consent to leukapheresis
• DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)
• DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis)

Exclusion Criteria:

• Current grade II to IV acute GVHD or extensive chronic GVHD
• Karnofsky score < 50%
• Lansky Play-Performance Score < 40
• Evidence of relapse or progression of disease after transplantation
• DONOR: Donor who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)
• DONOR: Pregnancy
• DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection
• DONOR: Recent immunization may require a delay

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Fred Hutchinson Cancer Research Center Other

Overall Clinical Trial Officials and Contacts

Brenda Sandmaier Principal Investigator Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00096161

Study ID Number: 1825.00

ClinicalTrials.gov Identifier: NCT00096161

Health Authority: United States: Federal Government