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

March 8, 2024 updated by: Marie Bleakley, Fred Hutchinson Cancer Center

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

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.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 >= 70 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 (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)
  • 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 donating outside of the United States of America (USA) or Germany

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

Correlative studies
Given IV
Other Names:
  • Abitrexate
  • Folex
  • Mexate
  • MTX
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate-AQ
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039
Undergo TBI
Other Names:
  • Whole-Body Irradiation
  • TOTAL BODY IRRADIATION
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • SH T 586
Given IV or PO
Other Names:
  • Prograf
  • Hecoria
  • FK 506
  • Fujimycin
  • Protopic
Given IV
Other Names:
  • Tepadina
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
  • 1,1',1''-Phosphinothioylidynetrisaziridine
  • Girostan
  • N,N', N''-Triethylenethiophosphoramide
  • Tespamine
  • Thio-Tepa
  • Thiofosfamide
  • Thiofozil
  • Thiophosphamide
  • Thiophosphoramide
  • Thiotef
  • Tifosyl
  • TIO TEF
  • Tio-tef
  • Triethylene Thiophosphoramide
  • Triethylenethiophosphoramide
  • Tris(1-aziridinyl)phosphine sulfide
  • WR 45312
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Other Names:
  • HSC
  • HSCT
  • allogeneic stem cell transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
  • Peripheral Stem Cell Transplant
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Graft Failure
Time Frame: Up to 5 years
Graft failure defined as failure to reach ANC of >500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to <100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure
Up to 5 years
Time to Discontinuation of Systemic Immunosuppression
Time Frame: 5 years post transplant
Measure the number of days to discontinuation of systemic immunosuppression (both including and excluding calcineurin inhibitors) in pediatric recipients of CD45RA+ T cell-depleted PBSCT. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)
5 years post transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion
Time Frame: Up to 5 years
Number of days post-transplant without transfusion where platelet count is >50,000/uL. Measured as the first of three days
Up to 5 years
Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion
Time Frame: Up to 5 years
Number of days post transplant until platelet count is >20,000/uL for three consecutive days without transfusion, counted as the first of three days
Up to 5 years
Time to ANC of > 1,000/uL
Time Frame: Up to 5 years
Time (in days) to ANC of > 1,000/uL, counted as the first of three consecutive days post-transplant
Up to 5 years
Time to ANC of > 500/uL
Time Frame: Up to 5 years
Time (in days) to ANC of > 500/uL, counted as the first of three consecutive days post-transplant
Up to 5 years
Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression
Time Frame: Up to 5 years
Number of patients with chronic GVHD defined using NIH criteria. Incidents requiring only calcineurin inhibitors will not be counted. If patients do not develop cGVHD after transplant but then relapse and then receive a donor lymphocyte infusion or antigen specific T cells as treatment, they will no longer be evaluable for the cGVHD endpoint.
Up to 5 years
Acute GVHD Grade III-IV
Time Frame: Up to day 100
Number of patients with acute GVHD grade III-IV
Up to day 100
Acute GVHD Grades II-IV
Time Frame: Up to day 100
Number of patients with acute GVHD grades II-IV
Up to day 100
Steroid Refractory Acute GVHD
Time Frame: Up to day 100
Presence of steroid refractory acute GVHD within the first 100 days post transplant
Up to day 100
Relapse Post-transplant
Time Frame: Up to 5 years
Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology
Up to 5 years
Transplant Related Mortality
Time Frame: Up to 5 years
Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse
Up to 5 years
Use of Additional Immune Suppressive Agents to Treat Chronic GVHD
Time Frame: Up to 5 years
Use of additional immune suppressive agents to treat chronic GVHD other than first line therapy. First line therapy is considered prednisone and tacrolimus/cyclosporin.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Marie Bleakley, Fred Hutch/University of Washington Cancer Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2014

Primary Completion (Actual)

January 30, 2023

Study Completion (Actual)

July 30, 2023

Study Registration Dates

First Submitted

May 15, 2013

First Submitted That Met QC Criteria

May 16, 2013

First Posted (Estimated)

May 21, 2013

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 8, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • 2660.00 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
  • NCI-2013-00958 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • 2660
  • K23CA154532 (U.S. NIH Grant/Contract)
  • RG9213077 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
  • R01HL121568 (U.S. NIH Grant/Contract)
  • 2P01CA018029 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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