Transplanting depleted donor stem cells in patients with Fanconi Anemia using a new conditioning treatment
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
This study is testing a new way to use donor stem cells for people with Fanconi Anemia by giving them a special treatment first to see if it helps their blood and immune system recover better and with fewer side effects.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 18 (estimated) |
| Ages | 2 Years and up |
| Sex | All |
| Sponsor | Stanford University Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Stanford, California) |
| Trial ID | NCT04784052 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to develop a novel cell therapy for patients with Fanconi Anemia by using depleted donor stem cells after conditioning with an experimental antibody treatment called JSP-191. The goal is to enhance hematopoietic and immune reconstitution while reducing toxicity compared to traditional chemotherapy methods. Participants will receive the conditioning regimen, followed by the stem cell infusion, and will be monitored for up to two years post-infusion to assess outcomes and side effects.
Who should consider this trial
Good fit: Ideal candidates include individuals aged 2 years and older diagnosed with Fanconi Anemia who have bone marrow failure and an available HLA-matched donor.
Not a fit: Patients without a diagnosis of Fanconi Anemia or those who do not have an appropriate donor may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a safer and more effective treatment option for patients with Fanconi Anemia.
How similar studies have performed: While this approach is innovative, similar studies using depleted stem cell transplants have shown promise, indicating potential for success.
Eligibility criteria
Show full inclusion / exclusion 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
Where this trial is running
Stanford, California
- Stanford University — Stanford, California, United States (Recruiting)
Study contacts
- Principal investigator: Rajni Agarwal, MD — Stanford University
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.