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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


Phase 2
14 Years
55 Years
Open (Enrolling)
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes

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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 CenterSeattle, Washington  98109
Yale University School of Medicine/Yale New Haven HospitalNew Haven, Connecticut  06520