A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
14 Years
55 Years
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes
Trial Information
A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD
OBJECTIVES:
Primary
- Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients
with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+
T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this
to relevant historical experience.
- Estimate the probability of graft failure in these patients.
Secondary
- Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these
patients.
- Estimate the probability of transplant-related mortality by day 100 in these patients.
- Estimate the probability of relapse in these patients.
- Estimate the probability and severity of chronic GVHD in these patients.
OUTLINE: This is a multicenter study.
- Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily
for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days
(Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to
-2.)
- Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem
cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on
day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per
cohort 1. If the rate of grade II-IV acute GVHD in the first 35 patients is
significantly reduced (compared to historical controls), subsequent patients are
enrolled in cohort 2.
- Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily
beginning on day -1 and continuing until day 50, followed by a standard taper in
the absence of grade II-IV acute GVHD.
- Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily
beginning on day -1 and continuing until day 30, followed by a rapid taper in the
absence of grade II-IV acute GVHD.
Patients are followed actively for at least 1 year post transplant.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- Acute lymphocytic leukemia (ALL) or acute myeloid leukemia (AML) in first or
subsequent remission
- ALL or AML in relapse or primary refractory ALL or AML with a circulating blast
count ≤ 10,000/mm^3
- Refractory anemia with excess blasts (RAEB) (RAEB-1 or RAEB-2) if the patient
has received induction chemotherapy within the past 60 days
- Appropriate candidate for allogeneic hematopoietic stem cell transplantation (HSCT)
- No CNS involvement refractory to intrathecal chemotherapy and/or standard
cranial-spinal radiotherapy
PATIENT CHARACTERISTICS:
- Age 14-55
- Creatinine < 1.5 mg/dL
- Cardiac ejection fraction > 45%
- DLCO corrected > 60% of predicted
- Total bilirubin < 2 times upper limit of normal (ULN) (unless attributed to Gilbert
syndrome)
- AST and ALT < 2 times ULN
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 12 months after
transplantation
- HIV negative
- No co-existing disease (other than leukemia or RAEB) that would limit life expectancy
to < 3 months
- No uncontrolled infection that, in the opinion of the consulting infectious disease
physician, would contraindicate myeloablative HSCT
- No other medical condition that would contraindicate HSCT
- No known hypersensitivity to tacrolimus
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior HSCT
- No concurrent participation in other experimental studies for the prevention of
graft-vs-host disease
DONOR CHARACTERISTICS:
- Genotypic or phenotypic HLA-identical related donor
- Able to donate peripheral blood stem cells
- Age > 14 years
- Applicable to male patients only: No female donors who have previously given birth to
a male child or have had a pregnancy beyond the first trimester miscarriage or
termination of pregnancy or nursing
- No donors who have received blood transfusions
- No CD45 Mutation with aberrant CD45RA isoform expression
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of grade II-IV acute graft-vs-host disease (GVHD)
Outcome Time Frame:
Start of study to day 100
Safety Issue:
Yes
Principal Investigator
Marie Bleakley, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Food and Drug Administration
Study ID:
FHCRC-2222.00
NCT ID:
NCT00914940
Start Date:
October 2009
Completion Date:
August 2020
Related Keywords:
- Graft Versus Host Disease
- Leukemia
- Myelodysplastic Syndromes
- graft versus host disease
- adult acute lymphoblastic leukemia in remission
- recurrent adult acute lymphoblastic leukemia
- childhood acute lymphoblastic leukemia in remission
- recurrent childhood acute lymphoblastic leukemia
- adult acute myeloid leukemia in remission
- recurrent adult acute myeloid leukemia
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- childhood acute myeloid leukemia in remission
- recurrent childhood acute myeloid leukemia
- childhood myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- refractory anemia with excess blasts
- de novo myelodysplastic syndromes
- secondary myelodysplastic syndromes
- Graft vs Host Disease
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Yale University School of Medicine/Yale New Haven Hospital | New Haven, Connecticut 06520 |
