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NCT Number: NCT04784052

Depleted Donor Stem Cell Transplant in Children and Adults With Fanconi Anemia After Being Conditioned With a Regimen Containing Briquilimab

The objective of this clinical trial is to develop a cell therapy for Fanconi Anemia which enables enhanced donor hematopoietic and immune reconstitution with decreased toxicity by transplanting depleted stem cells from a donor with and without using an experimental antibody treatment called JSP-191 as a part of conditioning. This experimental treatment will hopefully cause fewer side effects than chemotherapy (the current standard of care method).

Participants will be administered the conditioning regimen, are assessed until they receive the depleted stem cell infusion, and will be followed for up to 2 years after the cell infusion.

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Key information

Conditions

Fanconi Anemia Anemia Anemia, Aplastic Anemia, Hypoplastic, Congenital Bone Marrow Diseases Bone Marrow Failure Disorders Congenital Bone Marrow Failure Syndromes Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Repair-Deficiency Disorders Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Metabolic Diseases Nutritional and Metabolic Diseases

Age range

2 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Stanford University

Stanford, California, 94305, United States

Location status: Recruiting

Location contact

Rajni Agarwal, MD

CONTACT

[email protected]

650-725-9250

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

All patients must have:

  • Fanconi Anemia diagnosis as demonstrated by abnormal chromosome breakage studies with increased sensitivity to mitomycin-C (MMC) or diepoxybutane (DEB) and at least one mutation in a known Fanconi-associated gene
  • Bone marrow failure (defined by reduction in at least one cell line on two separate occasions at least one month apart (e.g., platelet count of <100,000 per cubic millimeter, hemoglobin <9 gm/dl and/or absolute neutrophil count (ANC) of <1000/mm)
  • Age of ≥2 years
  • Consenting ≥5/10 HLA-matched related or unrelated donor available for apheresis
  • Organ function defined as:
  • Serum Creatinine <2.0 mg/dL and corrected creatinine clearance/cystatin cL >60 mL/min/1.73m^2 without dialysis
  • Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) corrected for hemoglobin and volume, >50% predicted by pulmonary function tests (PFTs)
  • For patients unable to cooperate for PFTs, criteria are no evidence of dyspnea at rest, no exercise intolerance, and no requirement for supplemental oxygen with spO2 >93%
  • Shortening fraction of ≥29% or ejection fraction of ≥45% by echocardiogram
  • Serum total bilirubin of <4 x ULN
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN
  • Prothrombin time international normalized ratio (PT INR) and partial thromboplastin time (PTT) <1.5 x ULN
  • Life expectancy of at least 2 years
  • Patients of childbearing potential must be willing to use an effective contraceptive method for the duration of the peri-transplant conditioning through hematopoietic recovery
  • Patients and/or parents or legal guardians must be able to provide written informed consent and authorize use and disclosure of personal health information in accordance with Health Insurance Portability and Accountability Act

Exclusion criteria

  • Patients with available and consenting 10/10 HLA-identical sibling donor for apheresis
  • Patients with any acute or uncontrolled infections at the time of enrollment, including bacterial, fungal or viral
  • Patients who are seropositive for HIV-I/II or HTLV-I/II.
  • Patients receiving any other investigational agents or other biological, chemotherapy, or radiation therapy within 14 days of enrollment
  • Patients with any active malignancies, myelodysplastic syndrome or other concerns for high-risk bone marrow disease
  • Patients who received androgens in last 3 months
  • Pregnant or lactating women
  • Women who are nursing and do not wish to discontinue breastfeeding
  • Lansky/Karnofsky performance score <50%.
  • Any other medical condition or history that, in the opinion of the Principal Investigator, could pose a significant safety risk to the participant or jeopardize the integrity of the study
  • Patients who, in the opinion of the Principal Investigator, may not be able to comply with the safety monitoring requirements of the study

Treatment and study plan

JSP191

Drug

Participants will receive a single IV dose at start of conditioning

CliniMACS Prodigy System

Device

The device used to remove the αβ+T cells from donor stem cell transplant before being given to the recipient

Depleted Stem Cell Transplant

Biological

TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic cells will be administered by IV after completion of conditioning regimen.

Rabbit Anti-Thymoglobulin (rATG)

Biological

3 consecutive daily doses of rATG will be given by IV during conditioning

Cyclophosphamide

Drug

4 consecutive daily doses of cyclophosphamid will be given by IV during conditioning

Other names: Cytoxan

Fludarabine

Drug

4 consecutive daily doses of fludarabine will be given by IV during conditioning

Rituximab

Drug

1 dose of rituximab will be given at the end of conditioning

Primary outcomes

  1. Number of participants without grade 3 and 4 treatment-emergent adverse events (TEAEs) (infusion related reactions).

    Time frame: From start of conditioning regimen administration until cell infusion (up to 30 days)

    Recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  2. Number of participants without grade 3 and 4 treatment-emergent adverse events (TEAEs) (infusion related reactions) following infusion of TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic graft transplantation

    Time frame: Up to 2 years post-cell infusion

  3. Number of participants able to achieve donor engraftment

    Time frame: Assessed at Day +42 post-cell infusion

    Participants have achieved engraftment when absolute Neutrophil Count (ANC) is above 500/mm^3 for three consecutive laboratory values obtained on different days post cell transplantation with >1% CD15 donor chimerism

  4. Number of participants who are able to have donor engraftment persist at the same rate or better compared to alternative hematopoietic cell transplant regimens for this patient population

    Time frame: Assessed at Day +100 post-cell infusion

Secondary outcomes

  1. Serum concentration of JSP191

    Time frame: Prior to start of conditioning regimen, and 5 minutes, 4 hours, +2, +3, +4, +6, +8, +10 days after start of conditioning regimen, and day of cell infusion

    Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion

  2. Serum concentration of rATG

    Time frame: Prior to start of rATG infusion; 15 minutes after first, second, and third rATG infusion; day of cell infusion; and week +1, week +2 and week +12 post cell infusion

    Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion

  3. Serum concentration of fludarabine

    Time frame: Prior to start of fludarabine infusion, and 15 minutes, 1 hour, 3 hours, and 6 hours after the fludarabine infusion

    Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion

  4. Participants who do not develop mucositis

    Time frame: Start of conditioning regimen until +12 weeks post-cell infusion (up to 15 weeks)

    Mucositis incidence will be scored using the CTC criteria

  5. Participants who do not develop veno-occlusive disease (VOD)

    Time frame: Start of conditioning regimen until +12 weeks post-cell infusion (up to 15 weeks)

    VOD incidence will be scored using the Modified Seattle criteria

  6. Number of participants who achieve hematopoietic recovery

    Time frame: Up to 107 weeks (after start of conditioning regimen through Week +104 post-cell infusion)

    Hematopoietic recovery defined by hemoglobin >8g/dL and platelets >20k/dL without transfusion support achieved on 7 days post-graft transplantation documented on hematologic monitoring

  7. Number of participants who achieve donor engraftment

    Time frame: Weeks +1 through +104 post-cell infusion

    Engraftment measured as peripheral blood (total, CD15+, CD3+, CD19+, CD56+, and CD34+) and bone marrow (total and CD34+) chimerism by STR analysis

  8. Number of participants who achieve immunologic recovery

    Time frame: Weeks +1 through +104 post-cell infusion

    Immunologic recovery defined as >200/uL CD3+ T-cells and as assessed by percent and absolute numbers of T (CD3), B (CD19) and NK (CD56) cells by CBC differential studies and flow cytometry for lymphocyte lineages

  9. Number of participants who develop Grade I-IV acute graft-vs-host disease (GvHD)

    Time frame: Day +100 post-cell infusion

  10. Number of participants who develop chronic graft-vs-host disease (GvHD)

    Time frame: Day +100 through Week +104 post-cell infusion

  11. Number of participants who achieve disease-free survival

    Time frame: Up to 104 weeks (from time of cell infusion through Week +104)

    Disease-free defined by improved DEB-induced chromosomal breakage analysis in peripheral blood lymphocyte cultures

Sponsors and collaborators

Lead sponsor

Porteus, Matthew, MD

Other

Registry information

Official study title

TCRαβ+ T-cell/CD19+ B-cell Depleted Hematopoietic Grafts and a Reduced Intensity Preparative Conditioning Regimen Containing JSP191 (Briquilimab) to Achieve Engraftment and Blood Reconstitution in Patients With Fanconi Anemia

Important dates

Study start
2021
Primary completion
2027
Study completion
2028
First posted
Mar 5, 2021
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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