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

NCT01858740 | Completed Phase 2 Results DMC

• 7 other identifiers: 2660.00NCI-2013-009582660K23CA154532RG9213077R01HL1215682P01CA018029
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Graft Failure

  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

  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 Outcomes (11)

• Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion

  Up to 5 years

• Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion

  Up to 5 years

• Time to ANC of > 1,000/uL

  Up to 5 years

• Time to ANC of > 500/uL

  Up to 5 years

• Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression

  Up to 5 years

Study Arms (1)

Treatment (CD45RA+ T cell depleted PBSCT)

EXPERIMENTAL

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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation; Drug: Tacrolimus; Drug: Thiotepa; Radiation: Total-Body Irradiation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

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

Also known as: allogeneic stem cell transplantation, HSC, HSCT

Treatment (CD45RA+ T cell depleted PBSCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (CD45RA+ T cell depleted PBSCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CD45RA+ T cell depleted PBSCT)

Methotrexate DRUG

Given IV

Also known as: 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

Treatment (CD45RA+ T cell depleted PBSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

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

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (CD45RA+ T cell depleted PBSCT)

T Cell-Depleted Hematopoietic Stem Cell Transplantation BIOLOGICAL

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

Treatment (CD45RA+ T cell depleted PBSCT)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (CD45RA+ T cell depleted PBSCT)

Thiotepa DRUG

Given IV

Also known as: 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

Treatment (CD45RA+ T cell depleted PBSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

Treatment (CD45RA+ T cell depleted PBSCT)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 35007144 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Biphenotypic, Acute; Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute

Interventions

fludarabine phosphate; Methotrexate; merphos; Peripheral Blood Stem Cell Transplantation; Tacrolimus; Thiotepa; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Macrolides; Lactones; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Marie Bleakley, MD
• Organization: Fred Hutchinson Cancer Center

mbleakle@fredhutch.org

206-667-6572

Study Officials

• Marie Bleakley

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 15, 2013
• First Posted: May 21, 2013
• Study Start: April 10, 2014
• Primary Completion: January 30, 2023
• Study Completion: July 30, 2023
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2024-03

Locations

US (1)