Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT00096161 |
|
Recruitment Status :
Completed
First Posted : November 9, 2004
Results First Posted : May 4, 2017
Last Update Posted : January 31, 2020
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: Cyclosporine Drug: Mycophenolate Mofetil Drug: Pentostatin Biological: Therapeutic Allogeneic Lymphocytes | Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 36 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (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 |
| Actual Study Start Date : | May 2003 |
| Actual Primary Completion Date : | February 2015 |
| Actual Study Completion Date : | August 2015 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: pentostatin, DLI, mycophenolate mofetil, cyclosporine
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
Given PO
Other Names:
Drug: Mycophenolate Mofetil Given PO
Other Names:
Drug: Pentostatin Given IV
Other Names:
Biological: Therapeutic Allogeneic Lymphocytes Given IV
Other Name: Allogeneic Lymphocytes |
- Percentage Patients With 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, up to Day 112 ]
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.
- Incidence of Grade IV Acute GVHD [ Time Frame: Within 100 days after the last DLI ]
Clinical Stage of acute GVHD according to Organ System
Skin:
- - Maculopapular rash <25% of body surface
- - Maculopapular rash 25-50% of body surface
- - Maculopapular rash >50% body surface area or generalized erythroderma
- - Generalized erythroderma with bullous formation and desquamation
Liver:
- - Bilirubin 2-3 mg/dl
- - Bilirubin 3.1-6 mg/dl
- - Bilirubin 6.1-15 mg/dl
- - Bilirubin >15 mg/dl
Gut:
- - >500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD
- - >1000 -1500 mL diarrhea per day
- - >1500 mL diarrhea per day
- - >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
- Incidence of GVHD [ Time Frame: 1 year after DLI ]
Percentage patients with acute or chronic GVHD.
The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
- Incidence of Infections [ Time Frame: 100 days after DLI ]
- Incidence of Relapse/Progression [ Time Frame: 1 year after DLI ]
CML Acquisition of a new cytogenetic abnormality and/or development of accelerated phase or blast crisis. Criteria for accelerated phase: unexplained fever >38.3° C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, BM blasts and promyelocytes >20%.
AML, ALL, CMML >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia.
CLL Progressive disease: ≥1 of: physical exam/imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation.
NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions.
MM
≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ tx; or definite increase in the size/number of plasmacytomas or lytic bone lesions.
- Survival [ Time Frame: 1 year after DLI ]Percentage patients surviving.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00096161
| United States, Utah | |
| Huntsman Cancer Institute/University of Utah | |
| Salt Lake City, Utah, United States, 84112 | |
| LDS Hospital | |
| Salt Lake City, Utah, United States, 84143 | |
| United States, Washington | |
| VA Puget Sound Health Care System | |
| Seattle, Washington, United States, 98101 | |
| Fred Hutch/University of Washington Cancer Consortium | |
| Seattle, Washington, United States, 98109 | |
| Italy | |
| University of Torino | |
| Torino, Italy, 10126 | |
| Principal Investigator: | Brenda Sandmaier | Fred Hutch/University of Washington Cancer Consortium |
| Responsible Party: | Brenda Sandmaier, Principal Investigator, Fred Hutchinson Cancer Research Center |
| ClinicalTrials.gov Identifier: | NCT00096161 |
| Other Study ID Numbers: |
1825.00 NCI-2010-00230 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 1825.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ) P01CA078902 ( U.S. NIH Grant/Contract ) P30CA015704 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 9, 2004 Key Record Dates |
| Results First Posted: | May 4, 2017 |
| Last Update Posted: | January 31, 2020 |
| Last Verified: | January 2020 |
|
Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Myelogenous, Chronic, BCR-ABL Positive Waldenstrom Macroglobulinemia Multiple Myeloma Myeloproliferative Disorders Myelodysplastic-Myeloproliferative Diseases Graft vs Host Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Leukemia, Myeloid Leukemia, Lymphoid Leukemia, B-Cell Bone Marrow Diseases Hematologic Diseases Neoplasms, Plasma Cell Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hemorrhagic Disorders Cyclosporine Mycophenolic Acid |