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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01858740
First received: May 15, 2013
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

This phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing a subset of the T cells from the donor cells before transplant may stop this from happening.


Condition Intervention Phase
Accelerated Phase Chronic Myelogenous Leukemia
Acute Leukemias of Ambiguous Lineage
Acute Undifferentiated Leukemia
Blastic Phase Chronic Myelogenous Leukemia
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Chronic Myelogenous Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Refractory Anemia With Excess Blasts
Relapsing Chronic Myelogenous Leukemia
Radiation: total-body irradiation
Drug: thiotepa
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Biological: T cell-depleted hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Drug: tacrolimus
Drug: methotrexate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Time to discontinuation of systemic immunosuppression [ Time Frame: Time from transplant to the final discontinuation of all systemic immune suppression assessed up to 5 years ] [ Designated as safety issue: No ]
  • Graft failure defined as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days or irreversible decrease in ANC to < 100 after an established donor graft [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A true probability of graft failure of 10% will be considered excessive. If there is sufficient evidence to suggest that the true probability of graft failure exceeds 10%, the study will be stopped.

  • Time to ANC of > 500/uL [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to ANC of > 1,000/uL [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to platelet count > 20,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Time to platelet count > 50,000/uL for 3 days without transfusion [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence of chronic GHVD meeting NIH criteria and requiring systemic pharmacological immunosuppression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Use of additional immune suppressive agents other than first line therapy [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Presence of acute GVHD grades II-IV [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]
  • Presence of acute GVHD grade III-IV [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]
  • Presence of steroid refractory acute GVHD [ Time Frame: Up to day 100 ] [ Designated as safety issue: No ]
  • Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2013
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (CD45RA+ T cell depleted PBSCT)

CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -7, receive thiotepa 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 continuously or 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.

Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Biological: T cell-depleted hematopoietic stem cell transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Procedure: peripheral blood stem cell transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Prograf
Drug: methotrexate
Given IV
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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 continuously 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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
    • Other acute leukemia (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia)
  • Patient with a human leukocyte antigen (HLA)-identical (HLA-A, B, C, and ribonucleic acid [RNA] binding motif protein 45 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC
  • DONOR: HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC
  • DONOR: HLA-matched related donors >= 18 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
  • Creatinine > 1.5 mg/dl
  • Cardiac ejection fraction < 45%
  • Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of < 60% predicted; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is < 92% on room air
  • Patients who have liver function test (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 unless there is a clear precipitating factor (such as an azole, methotrexate, bactrim or another drug); 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 and patients with reversible drug-related transaminitis 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: 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
  • DONOR: 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)
  • DONOR: Unrelated donors residing outside of the United States of America (USA)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01858740

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Marie Bleakley    206-667-6572      
Principal Investigator: Marie Bleakley         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Marie Bleakley Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01858740     History of Changes
Other Study ID Numbers: 2660.00, NCI-2013-00958, 2660.00, K23CA154532, P30CA015704
Study First Received: May 15, 2013
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Anemia, Refractory
Blast Crisis
Leukemia, Myeloid, Accelerated Phase
Anemia, Refractory, with Excess of Blasts
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anemia
Myelodysplastic Syndromes
Cell Transformation, Neoplastic
Carcinogenesis
Neoplastic Processes
Pathologic Processes
Methotrexate
Fludarabine phosphate
Tacrolimus
Vidarabine
Fludarabine

ClinicalTrials.gov processed this record on October 19, 2014