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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00096161
First received: November 9, 2004
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Childhood Myelodysplastic Syndromes
Chronic Eosinophilic Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Chronic Phase Chronic Myelogenous Leukemia
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Juvenile Myelomonocytic Leukemia
Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
Nodal Marginal Zone B-cell Lymphoma
Noncontiguous Stage II Adult Burkitt Lymphoma
Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
Noncontiguous Stage II Adult Lymphoblastic Lymphoma
Noncontiguous Stage II Grade 1 Follicular Lymphoma
Noncontiguous Stage II Grade 2 Follicular Lymphoma
Noncontiguous Stage II Grade 3 Follicular Lymphoma
Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Previously Treated Myelodysplastic Syndromes
Primary Myelofibrosis
Secondary Acute Myeloid Leukemia
Secondary Myelodysplastic Syndromes
Splenic Marginal Zone Lymphoma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Drug: pentostatin
Biological: therapeutic allogeneic lymphocytes
Drug: mycophenolate mofetil
Drug: cyclosporine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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:

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia, Childhood Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Myeloid Leukemia, Childhood Acute Non Lymphoblastic Leukemia B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Chronic Neutrophilic Leukemia Follicular Lymphoma Hodgkin Lymphoma Hypereosinophilic Syndrome Juvenile Myelomonocytic Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphosarcoma Mantle Cell Lymphoma Multiple Myeloma Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myelofibrosis Plasmablastic Lymphoma
U.S. FDA Resources

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

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

  • 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 we 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.


Secondary Outcome Measures:
  • 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.

  • 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.

  • Disease response of the combined use of pentostatin and DLI [ Time Frame: Up to 12 years ] [ Designated as safety issue: No ]
  • Relapse/progression [ Time Frame: Up to 12 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to 12 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 80
Study Start Date: May 2003
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pentostatin, donor lymphocyte infusion (DLI)

* 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 once daily QD on days 0 to 27. Treatment continues in the absence of GvHD.

Drug: pentostatin
Given IV
Other Names:
  • 2'-deoxycoformycin
  • co-vidarabine
  • DCF
  • deoxycoformycin
  • Nipent
Biological: therapeutic allogeneic lymphocytes
Given IV
Other Name: ALLOLYMPH
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune

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. 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 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

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%
  • Lansky Play-Performance Score < 40
  • Evidence of relapse or progression of disease after transplantation
  • Prior recipient of cord blood
  • 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
  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 Completed
Salt Lake City, Utah, United States, 84112
LDS Hospital Completed
Salt Lake City, Utah, United States, 84143
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Brenda M. Sandmaier    206-667-4961      
Principal Investigator: Brenda M. Sandmaier         
VA Puget Sound Health Care System Recruiting
Seattle, Washington, United States, 98101
Contact: Thomas R. Chauncey    206-764-2709      
Principal Investigator: Thomas R. Chauncey         
Italy
University of Torino Recruiting
Torino, Italy, 10126
Contact: Benedetto Bruno    29-011-6334419      
Principal Investigator: Benedetto Bruno         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Brenda Sandmaier Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

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, P30CA015704, P01CA078902
Study First Received: November 9, 2004
Last Updated: July 28, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Blast Crisis
Burkitt Lymphoma
Hodgkin Disease
Hypereosinophilic Syndrome
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Acute
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, Neutrophilic, Chronic
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Neoplasm Metastasis

ClinicalTrials.gov processed this record on October 29, 2014