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

NCT04784052 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-60108
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fanconi Anemia

Keywords

Cell Transplants; Grafts; Stem Cells

Outcome Measures

Primary Outcomes (4)

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

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

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

• 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

  Up to 2 years post-cell infusion

• Number of participants able to achieve donor engraftment

  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

  Assessed at Day +42 post-cell infusion

• 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

  Assessed at Day +100 post-cell infusion

Secondary Outcomes (11)

• Serum concentration of JSP191

  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

• Serum concentration of rATG

  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

• Serum concentration of fludarabine

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

• Participants who do not develop mucositis

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

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

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

Study Arms (2)

Depleted Stem Cell Transplant with JSP-191 Conditioning

EXPERIMENTAL

Participants will receive an infusion of donor stem cells which have been depleted of αβ+T cells using the CliniMACS System device. Before the stem cell transplant, they will receive a reduced-intensity preparative regimen containing JSP191 in combination with rATG, cyclophosphamide, fludarabine and rituximab.

Drug: JSP191; Device: CliniMACS Prodigy System; Biological: Depleted Stem Cell Transplant; Biological: Rabbit Anti-Thymoglobulin (rATG); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Depleted Stem Cell Transplant without JSP-191 Conditioning

EXPERIMENTAL

Participants will receive an infusion of donor stem cells which have been depleted of αβ+T cells using the CliniMACS System device. Before the stem cell transplant, they will receive a reduced-intensity preparative regimen containing rATG, cyclophosphamide, fludarabine and rituximab.

Device: CliniMACS Prodigy System; Biological: Depleted Stem Cell Transplant; Biological: Rabbit Anti-Thymoglobulin (rATG); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Interventions

JSP191 DRUG

Participants will receive a single IV dose at start of conditioning

Depleted Stem Cell Transplant with JSP-191 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 with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Depleted Stem Cell Transplant BIOLOGICAL

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

Depleted Stem Cell Transplant with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Rabbit Anti-Thymoglobulin (rATG) BIOLOGICAL

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

Depleted Stem Cell Transplant with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Depleted Stem Cell Transplant with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Fludarabine DRUG

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

Depleted Stem Cell Transplant with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Rituximab DRUG

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

Depleted Stem Cell Transplant with JSP-191 Conditioning; Depleted Stem Cell Transplant without JSP-191 Conditioning

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Porteus, Matthew, MD: lead

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

RECRUITING

Related Publications (1)

• Agarwal R, Bertaina A, Soco C, Long-Boyle JR, Saini G, Kunte N, Hiroshima L, Chan YY, Willner H, Krampf MR, Nofal R, Barbarito G, Sen S, Van Hentenryck M, Walck E, Scheck A, Perriman RJ, Bouge A, Istomina E, Din HN, Klinger EF, Cheng JC, Wlodarski MW, Boelens JJ, Shizuru JA, Pang WW, Weinberg K, Parkman R, Roncarolo MG, Porteus M, Czechowicz A. Irradiation- and busulfan-free stem cell transplantation in Fanconi anemia using an anti-CD117 antibody: a phase 1b trial. Nat Med. 2025 Sep;31(9):3183-3190. doi: 10.1038/s41591-025-03817-1. Epub 2025 Jul 22.

  PMID: 40696207 DERIVED

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Cyclophosphamide; fludarabine; Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rajni Agarwal, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 5, 2021
• Study Start: December 7, 2021
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)