Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant
Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Accelerated Phase of Disease; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Myelodysplastic Syndrome; Chronic Eosinophilic Leukemia, Not Otherwise Specified; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase of Disease; de Novo Myelodysplastic Syndrome; DS Stage I Plasma Cell Myeloma; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone Lymphoma; Previously Treated Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Splenic Marginal Zone Lymphoma; Stage II Adult Non-Contiguous Immunoblastic Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage II Grade 3 Non-Contiguous Follicular Lymphoma; Stage II Marginal Zone Lymphoma; Stage II Non-Contiguous Adult Burkitt Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Mantle Cell Lymphoma; Stage II Small Lymphocytic Lymphoma; 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 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 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 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
Intervention: Pentostatin (Drug); Therapeutic Allogeneic Lymphocytes (Biological); Mycophenolate Mofetil (Drug); Cyclosporine (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: Fred Hutchinson Cancer Research Center Official(s) and/or principal investigator(s): Brenda Sandmaier, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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.
Clinical Details
Official title: Pentostatin and Donor Lymphocyte Infusion for Low Donor T-Cell Chimerism After Hematopoietic Cell Transplantation - A Multi-center Trial
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Safety of the combined use of pentostatin and DLI as defined by an acceptable rate of grade IV acute GVHDEfficacy of the combined use of pentostatin and DLI defined as an increase of at least 10 percentage points in donor T-cell chimerism
Secondary outcome: Incidence of grade II-IV acute GVHD infectionIncidence of grade II-IV acute GVHD infection Incidence of chronic GVHD infection Incidence of chronic GVHD infection Disease response of the combined use of pentostatin and DLI Relapse/progression Survival
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
University of Torino, Torino 10126, Italy; Recruiting Benedetto Bruno, Phone: 29-011-6334419 Benedetto Bruno, Principal Investigator
Huntsman Cancer Institute/University of Utah, Salt Lake City, Utah 84112, United States; Completed
LDS Hospital, Salt Lake City, Utah 84143, United States; Completed
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting Brenda M. Sandmaier, Phone: 206-667-4961 Brenda M. Sandmaier, Principal Investigator
VA Puget Sound Health Care System, Seattle, Washington 98101, United States; Recruiting Thomas R. Chauncey, Phone: 206-764-2709 Thomas R. Chauncey, Principal Investigator
Additional Information
Starting date: May 2003
Last updated: June 29, 2015
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