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

Brief Title

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 - A Multi-center Trial

Brief Summary

      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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism

Secondary Outcome

 Incidence of GVHD

Condition

Acute Lymphoblastic Leukemia

Intervention

Cyclosporine

Study Arms / Comparison Groups

 pentostatin, DLI, mycophenolate mofetil, cyclosporine

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

36

Start Date

May 2003

Completion Date

August 2015

Primary Completion Date

February 2015

Eligibility 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
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Brenda Sandmaier, , 

Location Countries

Italy

Location Countries

Italy

NCT ID

NCT00096161

Organization ID

1825.00

Secondary IDs

NCI-2010-00230

Responsible Party

Principal Investigator

Study Sponsor

Fred Hutchinson Cancer Center

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Brenda Sandmaier, Principal Investigator, Fred Hutch/University of Washington Cancer Consortium

Verification Date

January 2020