Stem Cell Transplant + JSP191 for Fanconi Anemia

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Porteus, Matthew, MD

Must not be taking: Investigational agents

Disqualifiers: HIV, Active infections, Malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for people with Fanconi Anemia, a condition that can lead to serious blood problems. The aim is to use a special antibody treatment, JSP191, to prepare the body for a stem cell transplant, potentially causing fewer side effects than current treatments like chemotherapy. Participants will receive this preparative treatment before receiving stem cells from a donor. This study may suit someone diagnosed with Fanconi Anemia who has experienced bone marrow failure and can find a partly matched stem cell donor. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works and measuring its effectiveness in an initial group, offering participants a chance to be among the first to benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken investigational agents, chemotherapy, or radiation therapy within 14 days before enrolling. Also, you cannot have used androgens in the last 3 months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the stem cell transplant is generally well-tolerated in patients with Fanconi Anemia. Studies have found a low occurrence of both short-term and long-term graft-versus-host disease (GVHD) and deaths unrelated to disease recurrence. This results in fewer complications and better survival chances for patients.

For JSP191, early results are encouraging. Initial findings from the first two patients with Fanconi Anemia showed complete donor cell engraftment, a positive outcome. Importantly, no treatment-related side effects were reported with JSP191.

Overall, both treatments appear to be safe options for patients. However, as this is a Phase 1/2 trial, researchers are still learning about their safety. This phase often gathers more safety information, so additional data will help confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining depleted stem cell transplant and JSP191 for Fanconi Anemia because it offers a novel approach that differs from typical treatments like androgen therapy and bone marrow transplants. Unlike standard methods, this treatment uses donor stem cells that are specifically depleted of αβ+T cells, potentially reducing the risk of graft-versus-host disease. Additionally, JSP191 is a unique conditioning agent that works with a reduced-intensity preparative regimen, which may be less toxic and more tolerable for patients with Fanconi Anemia. This innovative approach could offer a safer and more effective treatment option for this challenging condition.

What evidence suggests that this treatment might be an effective treatment for Fanconi Anemia?

In this trial, participants will receive a special type of stem cell transplant called TCRαβ/CD19-depleted, which research has shown can effectively treat certain non-cancerous blood disorders, such as Fanconi Anemia. Patients receiving these transplants often experience better recovery of their blood and immune cells. Additionally, the trial will use an experimental antibody called JSP191 during the preparation process. Studies have found that JSP191 can help the donor's cells completely replace the patient's cells without causing side effects. Early evidence suggests that JSP191 is safe and well-tolerated by patients with Fanconi Anemia. This treatment combination aims to provide a safer alternative to traditional chemotherapy, with fewer harmful side effects. ^{1 2 3 6 7}

Who Is on the Research Team?

Rajni Agarwal, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for children and adults with Fanconi Anemia, confirmed by specific tests and genetic mutations. Participants must be over 2 years old, have certain organ function levels (kidney, lung, heart), not be pregnant or breastfeeding, willing to use contraception if of childbearing potential, and have a life expectancy of at least 2 years. They should not have active cancers or uncontrolled infections.

Inclusion Criteria

My blood tests show low counts in at least one type of blood cell on two different tests a month apart.

Organ function criteria: 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), 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

I have a donor who matches at least half of my HLA markers for a cell donation.

Exclusion Criteria

I do not have any active cancers, myelodysplastic syndrome, or high-risk bone marrow diseases.

I need considerable assistance and medical care.

I haven't had any experimental treatments or other cancer therapies in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive a reduced-intensity preparative regimen containing JSP191 in combination with rATG, cyclophosphamide, fludarabine, and rituximab before the stem cell transplant

Up to 30 days

Stem Cell Infusion

Participants receive an infusion of donor stem cells depleted of αβ+T cells

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including hematopoietic and immunologic recovery

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Depleted Stem Cell Transplant
• JSP191

Trial Overview The trial is testing a new cell therapy using depleted stem cells from donors after conditioning with JSP191 antibody treatment. This aims to rebuild the patient's blood and immune systems with less toxicity than chemotherapy. Patients will undergo this regimen before receiving the stem cell infusion and will be monitored for up to two years.

How Is the Trial Designed?

Group I: Depleted Stem Cell Transplant with JSP-191 Conditioning Experimental Treatment 7 Interventions

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.

Who Is Running the Clinical Trial?

Porteus, Matthew, MD

Lead Sponsor

Trials

2

Recruited

30+

Maria Grazia Roncarolo

Lead Sponsor

Trials

1

Recruited

10+

Rajni Agarwal

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

In a study involving 33 children with high-risk acute myeloid leukemia (AML) who received TCR-alpha/beta and CD19-depleted grafts, primary engraftment was achieved in all patients, indicating the effectiveness of this graft manipulation method.

The cumulative incidence of acute graft-versus-host disease (aGvHD) was 39%, with a 10% transplant-related mortality rate, while the overall survival rate at 2 years was 67%, suggesting that this approach is both safe and effective for improving outcomes in pediatric AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia. Maschan, M., Shelikhova, L., Ilushina, M., et al.[2022]

A 10-year-old girl with Fanconi anemia successfully received a haploidentical bone marrow transplant (BMT) from her father after an initial transplant from her mother failed due to graft rejection, highlighting the potential for using family donors when matched donors are unavailable.

The transplant involved T cell depletion and did not require post-transplant immunosuppression, leading to a successful immunological reconstitution within 6 months without complications like graft-versus-host disease (GVHD) or severe infections, suggesting this method could be a preferred treatment for Fanconi anemia in similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful haploidentical bone marrow transplantation in Fanconi anemia. Elhasid, R., Ben Arush, MW., Katz, T., et al.[2004]

In a study of 34 patients with acute leukemia receiving αβ T-cell-depleted grafts from haploidentical donors, the approach showed promising results with low rates of severe graft-versus-host disease (GVHD) at 5.9% and a 1-year overall survival rate of 54%.

The study demonstrated that neutrophil and platelet engraftment occurred relatively quickly, on days 12 and 11 respectively, suggesting that this method may lead to faster recovery compared to other graft types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TcRαβ-depleted haploidentical transplantation results in adult acute leukemia patients. Kaynar, L., Demir, K., Turak, EE., et al.[2017]

Transplanting highly purified peripheral blood progenitor cells (PBPC) from alternative donors in 8 patients with Fanconi anemia resulted in a low incidence of graft-versus-host disease (GVHD), with only 2 cases of grade I acute GVHD and no chronic GVHD observed.

Despite some challenges, including two cases of secondary graft failure and three patient deaths, the overall survival rate at a median follow-up of 12 months was 58%, indicating that this method may improve transplant outcomes for patients with Fanconi anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low risk of graft-versus-host disease with transplantation of CD34 selected peripheral blood progenitor cells from alternative donors for Fanconi anemia. Boyer, MW., Gross, TG., Loechelt, B., et al.[2019]

A new 10-color quality control panel was developed to accurately quantify residual TCRαβ+ T cells and CD19+ B cells in stem cell grafts, which is crucial for preventing severe graft-versus-host disease (GvHD) after haploidentical stem cell transplantation (HSCT).

The immunomagnetic purification method achieved significant depletion of TCRαβ and CD19 cells, with recovery rates of 82.1% for stem cells, 67.1% for NK cells, and 72.7% for TCRγδ+ T cells, potentially improving transplantation outcomes by ensuring a safer graft composition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation and flow cytometric quality control of clinical-scale TCRαβ/CD19-depleted grafts. Bremm, M., Cappel, C., Erben, S., et al.[2017]

In a phase 2 trial involving 24 patients with Fanconi anemia, 91.6% achieved sustained primary engraftment after receiving T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation, with quick recovery times for neutrophils and platelets.

The treatment was well tolerated with no fatal transplant-related toxicities, and after a median follow-up of 5.2 years, the overall survival rate was 100%, indicating high efficacy and safety of this transplantation method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia. Strocchio, L., Pagliara, D., Algeri, M., et al.[2022]

A patient with Fanconi anemia successfully overcame severe rejection after a second allogeneic stem cell transplantation using antilymphocyte globulin followed by donor lymphocyte infusion, demonstrating a potential treatment strategy for this complication.

Three and a half years post-treatment, the patient is alive with a high Karnofsky score of 90% and has maintained donor-origin molecular chimerism, indicating effective engraftment and health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rejection of the second allogeneic graft in a child with Fanconi anemia reversed by antilymphocyte globulin and donor lymphocyte infusion. Abdelkefi, A., Ben Othman, T., Ladeb, S., et al.[2016]

Haplo-identical donors (HDs) provide better event-free survival (EFS) for Fanconi anemia patients undergoing hematopoietic cell transplantation (HCT) compared to HLA-mismatched unrelated donors (MMUD), especially when using unmanipulated grafts, with EFS rates of 86% versus 58%.

The study found that acute graft-versus-host disease (GVHD) rates were significantly lower in patients receiving T cell-depleted grafts from HDs (17%) compared to those from MMUD (41%) and unmanipulated HDs (40%), suggesting that T cell depletion may enhance safety in HCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: Results from the Severe Aplastic Anemia Working Party of the EBMT. Zubicaray, J., Pagliara, D., Sevilla, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04784052

Study Details | NCT04784052 | Depleted Donor Stem Cell ... The objective of this clinical trial is to develop a cell therapy for Fanconi Anemia which enables enhanced donor hematopoietic and immune reconstitution ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0966327425000486

Comprehensive up-to-date analysis on TCRαβ/CD19 ... This meta-analysis assesses the efficacy of TCRαβ+/CD19+ depleted hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematological ...

3. ashpublications.org ashpublications.org/bloodadvances/article/6/1/281/477111/TCR-CD19-depleted-HSCT-from-an-HLA-haploidentical

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical ... Key Points. TCRαβ/CD19-depleted HLA-haploidentical HSCT is an effective strategy for children with several nonmalignant disorders.

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper206381.html

Evaluation of Bone Marrow in Fanconi Anemia Patients ... 2015 Evaluation of Bone Marrow in Fanconi Anemia Patients Treated with Briquilimab Antibody-Based Conditioning and TCRαβ+ T-Cell/CD19+ B-Cell ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33656536/

HLA-haploidentical TCRαβ+/CD19+-depleted stem cell ... We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor ...

6. ashpublications.org ashpublications.org/blood/article/143/3/279/498045/TCR-CD19-cell-depleted-HLA-haploidentical

TCRαβ/CD19 cell–depleted HLA-haploidentical ... We showed that this type of transplant is characterized by a low incidence of both acute and chronic GVHD and nonrelapse mortality (NRM), ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12293416/

Hematopoietic Stem Cell Transplant in Adult Patients with ... Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), ...