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

NCT ID: NCT04784052

Last Updated: 2025-04-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-07
• Study Completion Date: 2027-12-31

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 after 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Depleted Stem Cell Transplant with JSP-191 Conditioning

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.

Group Type: EXPERIMENTAL

JSP191

Intervention Type: DRUG

Participants will receive a single IV dose at start of conditioning

CliniMACS Prodigy System

Intervention Type: 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

Intervention Type: BIOLOGICAL

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

Rabbit Anti-Thymoglobulin (rATG)

Intervention Type: BIOLOGICAL

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

Cyclophosphamide

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Interventions

JSP191

Participants will receive a single IV dose at start of conditioning

Intervention Type: DRUG

CliniMACS Prodigy System

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

Intervention Type: DEVICE

Depleted Stem Cell Transplant

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

Intervention Type: BIOLOGICAL

Rabbit Anti-Thymoglobulin (rATG)

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

Intervention Type: BIOLOGICAL

Cyclophosphamide

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

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: DRUG

Other Intervention Names

Cytoxan

Eligibility Criteria

Inclusion Criteria

All patients must have:

1. 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

2. 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)

3. Age of ≥2 years

4. Consenting ≥5/10 HLA-matched related or unrelated donor available for apheresis

5. Organ function defined as:

1. Serum Creatinine <2.0 mg/dL and corrected creatinine clearance/cystatin cL >60 mL/min/1.73m^2 without dialysis

2. 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)

3. 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%

4. Shortening fraction of ≥29% or ejection fraction of ≥45% by echocardiogram

5. Serum total bilirubin of <4 x ULN

6. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 x ULN

7. Prothrombin time international normalized ratio (PT INR) and partial thromboplastin time (PTT) <1.5 x ULN

6. Life expectancy of at least 2 years

7. Patients of childbearing potential must be willing to use an effective contraceptive method for the duration of the peri-transplant conditioning through hematopoietic recovery

8. 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

1. Patients with available and consenting 10/10 HLA-identical sibling donor for apheresis

2. Patients with any acute or uncontrolled infections at the time of enrollment, including bacterial, fungal or viral

3. Patients who are seropositive for HIV-I/II or HTLV-I/II.

4. Patients receiving any other investigational agents or other biological, chemotherapy, or radiation therapy within 14 days of enrollment

5. Patients with any active malignancies, myelodysplastic syndrome or other concerns for high-risk bone marrow disease

6. Patients who received androgens in last 3 months

7. Pregnant or lactating women

8. Women who are nursing and do not wish to discontinue breastfeeding

9. Lansky/Karnofsky performance score <50%.

10. 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

11. Patients who, in the opinion of the Principal Investigator, may not be able to comply with the safety monitoring requirements of the study

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Porteus, Matthew, MD

OTHER

Sponsor Role: lead

Responsible Party

Rajni Agarwal

Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajni Agarwal, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University

Stanford, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Rajni Agarwal, MD

Role: primary

scgt_clinical_trials_office@lists.stanford.edu

650-725-9250

References

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.

Reference Type: DERIVED

PMID: 40696207 (View on PubMed)

Other Identifiers

IRB-60108

Identifier Type: -

Identifier Source: org_study_id