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A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children


Phase 2
N/A
21 Years
Not Enrolling
Both
Accelerated Phase Chronic Myelogenous Leukemia, Blastic Phase Chronic Myelogenous Leukemia, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Childhood Chronic Myelogenous Leukemia, Graft Versus Host Disease, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts, Relapsing Chronic Myelogenous Leukemia

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Trial Information

A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children


PRIMARY OBJECTIVES:

I. Estimate the time to discontinuation of systemic immunosuppression in pediatric
recipients of cluster of differentiation 45RA positive (CD45RA+) T cell-depleted peripheral
blood stem cell transplant (PBSCT).

II. Estimate the probability of graft failure in pediatric recipients of CD45RA+
T-cell-depleted PBSCT.

SECONDARY OBJECTIVES:

I. Estimate and compare to an appropriate historical cohort the probability of chronic
graft-versus-host disease (GVHD) (National Institutes of Health [NIH] criteria) requiring
treatment with systemic pharmacological immunosuppression in pediatric patients who receive
CD45RA+ T cell depleted PBSC.

II. Estimate the probability of acute GVHD grade II-IV.

III. Estimate the probability of steroid refractory acute GVHD.

IV. Evaluate immune reconstitution.

V. Estimate the probability of transplant-related mortality by day 100.

VI. Estimate the probability of relapse.

OUTLINE:

CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on
days -10 to -7, receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and
fludarabine phosphate IV over 30 minutes on days -6 to -2.

TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day
0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV hours or orally (PO) every
12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive
methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up for up to 5 years.


Inclusion Criteria:



- Patients who are considered appropriate candidates for allogeneic hematopoietic stem
cell transplantation and have one of the following diagnoses:

- Acute lymphocytic leukemia in first or subsequent remission

- Acute myeloid leukemia in first or subsequent remission

- Acute lymphocytic leukemia in relapse or primary refractory disease with a
circulating blast count of no more than 10,000/mm^3

- Acute myeloid leukemia in relapse or primary refractory disease with a
circulating blast count of no more than 10,000/mm^3

- Refractory anemia with excess blasts (RAEB-1 and RAEB-2)

- Chronic myelogenous leukemia with a history of accelerated phase or blast crisis

- Patient with a human leukocyte antigen (HLA)-identical (HLA-A, B, C, and DRB1
molecularly matched) unrelated donor or related donor capable of donating PBSC

- DONOR SELECTION INCLUSION

- HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution
typing) capable and willing to donate PBSC

- HLA-matched related donors >= 14 years and capable and willing to donate PBSC

Exclusion Criteria:

- Patients with central nervous system (CNS) involvement refractory to intrathecal
chemotherapy and/or standard cranial-spinal radiation

- Patients on other experimental protocols for prevention of acute GVHD

- Patients who weigh >= 60 kg must be discussed with the principal investigator prior
to enrolling on the protocol

- Patients who are human immunodeficiency virus positive (HIV+)

- Patients with uncontrolled infections for whom myeloablative hematopoietic stem cell
transplant (HCT) is considered contraindicated by the consulting infectious disease
physician

- Patients with organ dysfunction

- Renal insufficiency (creatinine > 1.5 mg/dl)

- Cardiac ejection fraction < 45%

- Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 60%

- Liver function abnormality; patients who have liver function tests (LFTs)
(including total bilirubin, aspartate aminotransferase [AST] and alanine
aminotransferase [ALT]) >= twice the upper limit of normal should be evaluated
by a gastrointestinal (GI) physician; if the GI physician considers that HCT on
protocol 2660 is contraindicated for that patient the patient will be excluded
from the protocol; patients with Gilbert's syndrome and no other known liver
function abnormality do not necessarily require GI consultation and may be
included on the protocol

- Patients with a life expectancy < 3 months from co-existing disease other than the
leukemia or RAEB

- Patients who are pregnant or breast-feeding

- Fertile patients of child bearing age unwilling to use contraception during and for
12 months post transplant

- Patients with a significant other medical conditions that would make them unsuitable
for transplant

- Patients with a known hypersensitivity to tacrolimus

- DONOR SELECTION EXCLUSION

- Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive
or with active hepatitis B or hepatitis C virus infection

- Donors who fail eligibility requirements for donation of cells or tissue per section
21 Code of Federal Regulations (CFR) 1271 for donation of a HCT/product (P) will be
excluded unless use of the cells complies with 21 CFR 1271.65(b)(iii) (urgent medical
need) or with 21 CFR 1271.65(b)(i) (allogeneic use in a first-degree or second-degree
relative)

- Unrelated donors residing outside of the United States of America (USA)

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Outcome Measure:

Time to discontinuation of systemic immunosuppression

Outcome Time Frame:

Time from transplant to the final discontinuation of all systemic immune suppression assessed up to 5 years

Safety Issue:

No

Principal Investigator

Marie Bleakley

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2660.00

NCT ID:

NCT01858740

Start Date:

June 2013

Completion Date:

Related Keywords:

  • Accelerated Phase Chronic Myelogenous Leukemia
  • Blastic Phase Chronic Myelogenous Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Childhood Acute Myeloid Leukemia in Remission
  • Childhood Chronic Myelogenous Leukemia
  • Graft Versus Host Disease
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Myeloid Leukemia
  • Refractory Anemia With Excess Blasts
  • Relapsing Chronic Myelogenous Leukemia
  • Anemia
  • Anemia, Refractory
  • Anemia, Refractory, with Excess of Blasts
  • Blast Crisis
  • Graft vs Host Disease
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Hematologic Neoplasms

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109