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

NCT00096161 | Completed Phase 2 Results DMC

• 4 other identifiers: 1825.00NCI-2010-00230P01CA078902P30CA015704
• Study Type: interventional
• Target: 36
• Locations: 2 countries
• Sites: 5

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

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

  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. "Chimerism" in hematopoietic cell transplant derives from this idea of a "mixed" entity, referring to someone who has received a transplant of genetically different tissue. A test for chimerism after a hematopoietic cell transplant involves identifying the genetic profiles of the recipient and of the donor and then evaluating the extent of mixture in the recipient's blood cells or marrow cells.

  From the time of enrollment maintained to day 56 after the last DLI, up to Day 112

• Incidence of Grade IV Acute GVHD

  Clinical Stage of acute GVHD according to Organ System Skin: 1. \- Maculopapular rash \<25% of body surface 2. \- Maculopapular rash 25-50% of body surface 3. \- Maculopapular rash \>50% body surface area or generalized erythroderma 4. \- Generalized erythroderma with bullous formation and desquamation Liver: 1. \- Bilirubin 2-3 mg/dl 2. \- Bilirubin 3.1-6 mg/dl 3. \- Bilirubin 6.1-15 mg/dl 4. \- Bilirubin \>15 mg/dl Gut: 1. \- \>500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD 2. \- \>1000 -1500 mL diarrhea per day 3. \- \>1500 mL diarrhea per day 4. \- \>1500 mL diarrhea per day plus severe abdominal pain with or without ileus Overall Clinical Grading of Severity of acute GVHD Grade IV: 0-4 Skin, 2-4 Liver, and/or 2-4 GI

  Within 100 days after the last DLI

Secondary Outcomes (4)

• Incidence of GVHD

  1 year after DLI

• Incidence of Infections

  100 days after DLI

• Incidence of Relapse/Progression

  1 year after DLI

• Survival

  1 year after DLI

Study Arms (1)

pentostatin, DLI, mycophenolate mofetil, cyclosporine

EXPERIMENTAL

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; Drug: Mycophenolate Mofetil; Drug: Pentostatin; Biological: Therapeutic Allogeneic Lymphocytes

Interventions

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

pentostatin, DLI, mycophenolate mofetil, cyclosporine

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

pentostatin, DLI, mycophenolate mofetil, cyclosporine

Pentostatin DRUG

Given IV

Also known as: (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

pentostatin, DLI, mycophenolate mofetil, cyclosporine

Therapeutic Allogeneic Lymphocytes BIOLOGICAL

Given IV

Also known as: Allogeneic Lymphocytes

pentostatin, DLI, mycophenolate mofetil, cyclosporine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

University of Torino

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Graft vs Host Disease; Hodgkin Disease; Myelodysplastic-Myeloproliferative Diseases; Lymphoma, Non-Hodgkin; Multiple Myeloma; Waldenstrom Macroglobulinemia

Interventions

Cyclosporine; Cyclosporins; Mycophenolic Acid; Pentostatin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Bone Marrow Diseases; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Coformycin; Formycins; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Brenda M. Sandmaier
• Organization: Fred Hutchinson Cancer Research Center

bsandmai@fhcrc.org

(206) 667-4961

Study Officials

• Brenda Sandmaier

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 9, 2004
• First Posted: November 9, 2004
• Study Start: May 1, 2003
• Primary Completion: February 1, 2015
• Study Completion: August 1, 2015
• Last Updated: January 31, 2020
• Results First Posted: May 4, 2017

Record last verified: 2020-01

Locations

IT (1); US (4)