test

Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

Conditions

Graft Versus Host Disease | Leukemia | Myelodysplastic Syndromes

Trial Phase

Phase 2

Trial Purpose and Description

Trial Purpose


RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure
acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body
irradiation to stop the growth of cancer and remove the patient's diseased bone marrow,
healthy stem cells from a donor are infused into the patient to replace the patient's bone
marrow and make red and white blood cells and platelets. Unfortunately HSCT is often
complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a
donor can make an immune response against the body's normal cells and cause tissue damage
and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before
transplant may reduce the frequency and intensity of GVHD.

PURPOSE: This phase II trial will determine whether the removal of the naive T cells from
donor cells can decrease the rate and severity of graft-vs-host disease while preserving
specific immunity against infections in patients with acute leukemia or advanced
myelodysplastic syndromes.

Trial Description


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.

Participation Guidelines

Age:
14 Years - 55 Years
Gender:
Both

Eligibility 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
Sponsor:
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Yale University
Dates:
October 2009
Last Updated:
June 12, 2014
Study HIC#:

Clinicaltrials.gov ID: NCT00914940