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

NCT ID: NCT01858740

Last Updated: 2024-03-12

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-04-10

Study Completion Date

2023-07-30

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Biphenotypic Leukemia Acute Leukemia of Ambiguous Lineage Acute Undifferentiated Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Chronic Myelogenous Leukemia, BCR-ABL1 Positive Myelodysplastic Syndrome With Excess Blasts-1 Myelodysplastic Syndrome With Excess Blasts-2 Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Adult Acute Myeloid Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Recurrent Childhood Acute Myeloid Leukemia Refractory Adult Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Methotrexate

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Intervention Type BIOLOGICAL

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Tacrolimus

Intervention Type DRUG

Given IV or PO

Thiotepa

Intervention Type DRUG

Given IV

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Interventions

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Allogeneic Hematopoietic Stem Cell Transplantation

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Intervention Type PROCEDURE

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Methotrexate

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Intervention Type PROCEDURE

T Cell-Depleted Hematopoietic Stem Cell Transplantation

Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Intervention Type BIOLOGICAL

Tacrolimus

Given IV or PO

Intervention Type DRUG

Thiotepa

Given IV

Intervention Type DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Other Intervention Names

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

Eligibility Criteria

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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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Marie Bleakley

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Marie Bleakley

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10.

Reference Type DERIVED
PMID: 35007144 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2013-00958

Identifier Type: REGISTRY

Identifier Source: secondary_id

2660

Identifier Type: -

Identifier Source: secondary_id

2660.00

Identifier Type: OTHER

Identifier Source: secondary_id

K23CA154532

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG9213077

Identifier Type: OTHER

Identifier Source: secondary_id

R01HL121568

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2P01CA018029

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2660.00

Identifier Type: -

Identifier Source: org_study_id

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