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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 GVHD

Efficacy 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 infection

Incidence 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

Page last updated: August 23, 2015

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