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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00096161
First received: November 9, 2004
Last updated: February 29, 2016
Last verified: January 2016
  Purpose
This phase II 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.

Condition Intervention Phase
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Chronic Lymphocytic Leukemia
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Graft Versus Host Disease
Hodgkin Lymphoma
Myelodysplastic/Myeloproliferative Neoplasm
Non-Hodgkin Lymphoma
Plasma Cell Myeloma
Waldenstrom Macroglobulinemia
Drug: Cyclosporine
Drug: Mycophenolate Mofetil
Drug: Pentostatin
Biological: Therapeutic Allogeneic Lymphocytes
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pentostatin and Donor Lymphocyte Infusion for Low Donor T-cell Chimerism After Hematopoietic Cell Transplantation - A Multi-center Trial

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then it can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements.

  • 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 ] [ Designated as safety issue: Yes ]
    Reported following the Fred Hutchinson Cancer Research Center (FHCRC) Guidelines for serious adverse event (SAE) reporting.


Secondary Outcome Measures:
  • Disease response of the combined use of pentostatin and DLI [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Incidence of chronic GVHD infection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    Reported following the FHCRC Guidelines for SAE reporting.

  • Incidence of chronic GVHD infection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Reported following the FHCRC Guidelines for SAE reporting.

  • Incidence of grade II-IV acute GVHD infection [ Time Frame: Day 84 ] [ Designated as safety issue: No ]
    Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.

  • Incidence of grade II-IV acute GVHD infection [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.

  • Relapse/progression [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]

Enrollment: 37
Study Start Date: May 2003
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pentostatin, DLI, mycophenolate mofetil, cyclosporine

Group I (pentostatin, DLI): Patients receive pentostatin 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 CD3-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 (pentostatin, DLI, mycophenolate mofetil, cyclosporine): Patients receive treatment as in group I. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD.

Drug: Cyclosporine
Given PO
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Drug: Pentostatin
Given IV
Other Names:
  • (R)-3-(2-Deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7, 8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol
  • 2'-Deoxycoformycin
  • CI-825
  • Co-Vidarabine
  • Covidarabine
  • DCF
  • Deoxycoformycin
  • Nipent
  • PD-81565
  • Pentostatine
Biological: Therapeutic Allogeneic Lymphocytes
Given IV
Other Name: Allogeneic Lymphocytes

Detailed Description:

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 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.

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 cyclosporine orally (PO) twice daily (BID) on days -3 to 56 and mycophenolate mofetil PO once daily (QD) 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.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients having received a preceding allogeneic transplantation from either a human leukocyte antigen (HLA)-matched related or unrelated donor are eligible for this protocol

    • Related donor: HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA A, B, C, DRB1, and DQB1
    • Unrelated donor who are prospectively:

      • Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR
      • Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
  • 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
  • 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%

    • Pediatric criteria

      • Lansky play-performance score < 40
  • Evidence of relapse or progression of disease after transplantation
  • Prior recipient of cord blood
  • DONOR: Donors 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00096161

Locations
United States, Utah
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States, 84112
LDS Hospital
Salt Lake City, Utah, United States, 84143
United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98101
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Italy
University of Torino
Torino, Italy, 10126
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Brenda Sandmaier Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00096161     History of Changes
Other Study ID Numbers: 1825.00  NCI-2010-00230  1825.00  P01CA078902  P30CA015704 
Study First Received: November 9, 2004
Last Updated: February 29, 2016
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Lymphocytic, Chronic, B-Cell
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, Non-Hodgkin
Graft vs Host Disease
Waldenstrom Macroglobulinemia
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bone Marrow Diseases
Hematologic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders

ClinicalTrials.gov processed this record on July 27, 2016