Acute Lymphoblastic LeukemiaPhase 2NCT00096161
Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant
A Phase 2 study testing Cyclosporine, Mycophenolate Mofetil and Pentostatin in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by Fred Hutchinson Cancer Center at 5 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia
- What is being tested?
- Cyclosporine, Mycophenolate Mofetil and Pentostatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 5 sitesin 2 countries
- Study dates
- May 2003to Aug 2015
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 14Show fewer
- 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)
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
LDS Hospital
Salt Lake City, Utah, 84143
VA Puget Sound Health Care System
Seattle, Washington, 98101
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Pentostatin and Donor Lymphocyte Infusion for Low Donor T-cell Chimerism After Hematopoietic Cell Transplantation - A Multi-center Trial
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Lymphocytic Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Graft Versus Host Disease, Hodgkin Lymphoma
- Being tested
- Cyclosporine, Mycophenolate Mofetil, Pentostatin, Therapeutic Allogeneic Lymphocytes
- Medical subject headings
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called 27-400, Ciclosporin, CsA, Cyclosporin
Given PO
Also called Cellcept, MMF
Given PO
PentostatinDrug
Also called (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
Given IV
Therapeutic Allogeneic LymphocytesBiological
Also called Allogeneic Lymphocytes
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: Pentostatin; Biological: Therapeutic Allogeneic Lymphocytes |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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:
- - 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
Measured: Within 100 days after the last DLI
Secondary outcomes (4)
Incidence of GVHD
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.
Measured: 1 year after DLI
Incidence of Infections
Measured: 100 days after DLI
Incidence of Relapse/Progression
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.
Measured: 1 year after DLI
Survival
Percentage patients surviving.
Measured: 1 year after DLI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2004 (estimated)
- Study startMay 2003
- Primary completionFeb 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Brenda Sandmaier, Fred Hutchinson Cancer Center
- Investigators
- Brenda Sandmaier, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00096161
- Sponsor's protocol ID
- 1825.00
- Other IDs
- NCI-2010-00230, 1825.00, P01CA078902, P30CA015704
- Status last verified
- Jan 2020
- First submitted
- 9 Nov 2004
- Last updated
- 31 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes