Unrelated And Partially Matched Related Donor PSCT w/ T Cell Receptor (TCR) αβ Depletion for Patients With BMF

NCT03047746 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 16-012881
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and inherited bone marrow failure (BMF) syndromes.

Conditions

Acquired Aplastic Anemia; Paroxysmal Nocturnal Hemoglobinuria; Inherited Bone Marrow Failure Syndromes

Outcome Measures

Primary Outcomes (4)

• Rate of graft failure

  Up to three years post-transplantation

• Time to neutrophil engraftment

  Up to 60 days post-transplantation

• Incidence of acute graft vs. host disease (GVHD)

  Up to 100 days post-transplantation

• Incidence of chronic graft vs. host disease (GVHD)

  Up to three years post-transplantation

Secondary Outcomes (4)

• Treatment-related Mortality (TRM)

  Up to 100 days post-transplantation

• Probability of event-free survival (EFS)

  Up to 1 year post-transplantation

• Probability of overall survival (OS)

  Up to 1 year post-transplantation

• Reactivation/Infection from CMV, EBV, adenovirus

  Up to 1 year post-transplantation

Study Arms (3)

TCRalpha/beta Tcell Depletion for BMF with trilineage aplasia

OTHER

Patients with acquired or inherited bone marrow failure (iBMF) with trilineage aplasia excluding Fanconi Anemia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

Device: CliniMACs

TCRalpha/beta Tcell Depletion for BMF w/o trilineage aplasia

OTHER

Patients with acquired or inherited bone marrow failure (iBMF) without trilineage aplasia will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

Device: CliniMACs

TCRalpha/beta Tcell Depletion for BMF w/ Fanconi Anemia

OTHER

Patients with acquired or inherited bone marrow failure (iBMF) with Fanconi Anemia and related DNA Repair Disorders will be given previously established, disease-specific chemotherapy and/or radiation based conditioning regimens prior to hematopoietic stem cell transplantation using TCRalpha/beta and B cell depleted peripheral blood stem cells from unrelated or partially matched related donors.

Device: CliniMACs

Interventions

CliniMACs DEVICE

Peripheral blood stem cells from closely matched unrelated or partially matched related donors will be processed using the CliniMACS device to remove TCRalpha/beta T cells and B cells, in accordance with the Investigator Brochure and Technical Manual following the laboratory standard operating procedures (SOPs) and using aseptic technique

TCRalpha/beta Tcell Depletion for BMF w/ Fanconi Anemia; TCRalpha/beta Tcell Depletion for BMF w/o trilineage aplasia; TCRalpha/beta Tcell Depletion for BMF with trilineage aplasia

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Acquired and Inherited Bone Marrow Failure Conditions Associated with Trilinear Bone Marrow Failure
• Acquired Aplastic Anemia
• Must meet criteria for severe or very severe aplastic anemia (AA), defined by:
• i. Bone marrow biopsy demonstrating cellularity of \<25% overall or bone marrow biopsy that is overall hypocellular for age by pathology report with reductions in any two hematopoietic lineages (myeloid, erythroid, or megakaryocyte)
• ii. In addition, 2 of the following must be met:
• absolute neutrophil count (ANC) \< 500/µL (severe) or \< 200/µL (very severe). Current ANC or last ANC prior to start of Granulocyte-colony stimulating factor (G-CSF) may be used.
• platelets \< 30,000/µL or transfusion dependence
• absolute reticulocyte count \< 40,000/µL
• iii. Negative evaluation for inherited bone marrow failure conditions (see below)
• iv. Must not have accompanying diagnosis of myelodysplastic syndrome
• Patients meeting other eligibility criteria may receive study therapy as the initial treatment approach provided an eligible unrelated or mismatched related ("haplo") donor is available
• Patients who have received prior immune suppression therapy will be eligible if they have refractory or relapsed disease defined as per treating clinician's judgement, at least 12 weeks after initiation of immune suppression therapy. Relapsed patients who previously met hematologic criteria for severe aplastic anemia do not have to meet these hematologic criteria for severe aplastic anemia at time of relapse to be eligible for transplant.
• Paroxysmal Nocturnal Hemoglobinuria
• Patients must have testing (eg. Flow Cytometry demonstrating cells with absent cluster of differentiation 55 (CD55) or cluster of differentiation 59 (CD59) expression demonstrating a PNH clone in greater than 10% of peripheral blood red blood cells and/or granulocytes, along with clinical or laboratory evidence of intravascular hemolysis, such as:
• i. Elevated Lactate dehydrogenase (LDH)

You may not qualify if:

• Patients who do not meet disease, organ or infectious criteria.
• Patients with a clinical diagnosis of myelodysplastic syndrome (MDS) defined by combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7, Trisomy 8 eg.), with or without excess blasts.
• Patients with no suitable closely Human leukocyte antigen (HLA)-matched unrelated or related haploidentical matched donor available. Patients with suitable fully matched related donor are also not eligible.
• Pregnant females. All females of childbearing potential must have negative pregnancy test.
• Donor selection and eligibility:
• Donor selection will comply with 21 Code of Federal Regulations (CFR 1271) of the U.S. Food and Drug Administration's Code of Federal Regulations
• Donor testing:
• Unrelated donor meets National Marrow Donor Program criteria for donation
• For partially matched related donors, Children's Hospital of Philadelphia (CHOP) bone marrow transplant (BMT) standard procedures apply for determining donor eligibility, including donor screening and testing for relevant communicable disease agents and diseases. The donor collection program is FACT accredited.
• For partially matched related donors, if subject has genetically confirmed iBMF syndrome, related donor must be evaluated for this disorder and testing must be negative
• Infectious disease testing of donor will be per current Blood and Marrow Transplant Program Standards of Practice as per 21 CFR Part 1271. Donor medical records and history are reviewed to confirm that the donor is free of infectious risk factors and meets donor eligibility criteria as defined by 21 CFR 127.
• Donor matching
• High resolution HLA typing at HLA-A, -B, -C, DRB1, and DQB1 loci
• Unrelated donor
• Donor must be an antigen and allele match at ≥ 8/10 HLA Loci

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal; Congenital Bone Marrow Failure Syndromes

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Bone Marrow Failure Disorders; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Timothy Olson, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Timothy Olson M.D. Ph.D., Assistant Professor Pediatrics

Study Record Dates

• First Submitted: February 7, 2017
• First Posted: February 9, 2017
• Study Start: February 1, 2017
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)