JSP191 Conditioning for Immunodeficiency

Overseen By Lisa A Duncan, R.N.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Hematologic malignancy, Active malignancy, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to make stem cell transplants safer for individuals with GATA2 deficiency, a condition that weakens the immune system and can lead to serious infections and blood cancers. Researchers are testing a new drug, JSP191 (also known as Briquilimab), to determine if it can enhance the safety of these transplants by preparing the body to accept new stem cells. Participants will receive a series of treatments, including Briquilimab and other medications, to help prevent side effects. This trial may suit those aged 6 to 70 with GATA2 deficiency who experience frequent infections. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that Briquilimab, also known as JSP191, has been tested in various patient groups, including those with severe combined immunodeficiency (SCID) and myelodysplastic syndrome (MDS). In these studies, Briquilimab was generally well-tolerated. Specifically, a study with 24 patients who had MDS or acute myeloid leukemia reported no serious side effects linked to the treatment, suggesting the drug usually does not cause major side effects.

In another study involving 14 SCID patients, Briquilimab was part of a preparation process for transplants and was found to be safe. These results are promising for its use in making stem cell transplants safer for individuals with conditions like GATA2 deficiency. While this information supports Briquilimab’s safety, it is important to remember that each patient’s experience can vary, and ongoing research will provide more details. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about JSP191 for immunodeficiency because it offers a novel approach compared to traditional conditioning treatments. Unlike standard options that typically rely heavily on chemotherapy and radiation alone, JSP191 incorporates briquilimab, an antibody that targets specific immune cells. This targeted action could potentially reduce the harsh side effects usually associated with conditioning regimens. By combining briquilimab with traditional agents like fludarabine and total body irradiation (and cyclophosphamide in one arm), the hope is to enhance effectiveness while minimizing toxicity, making the treatment more tolerable and potentially safer for patients.

What evidence suggests that this trial's treatments could be effective for GATA2 deficiency?

Research has shown that Briquilimab, also known as JSP191, holds promise as a preparation treatment for stem cell transplants. In studies with patients who have sickle cell disease, those treated with Briquilimab received new stem cells quickly, with the new cells starting to grow in 12-16 days. Previous patients with severe combined immunodeficiency (SCID) also experienced positive results with this treatment. In this trial, participants in Arm A will receive Briquilimab, Fludarabine, and Total Body Irradiation, while those in Arm B will receive Briquilimab, Fludarabine, Cyclophosphamide, and Total Body Irradiation. Briquilimab has been well tolerated, with no severe side effects reported in 24 patients with other blood disorders. Its ability to prepare the body for new stem cells could make transplants safer for those with GATA2 deficiency. ^{2 3 5 6 7}

Who Is on the Research Team?

Danielle E Pregent-Arnold, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for people aged 6-70 with GATA2 deficiency, a condition affecting immune function and increasing cancer risk. Eligible participants must have certain blood cell counts, organ function within specific limits, and an available matched stem cell donor. They should be able to stay near the hospital for at least 100 days post-transplant with a caregiver.

Inclusion Criteria

I have a harmful GATA2 gene mutation.

I am between 6 and 70 years old.

Clinical manifestation(s) consistent with a diagnosis of GATA2 deficiency, including history of severe, disfiguring, and/or recurrent infections, low monocyte, B cell, and/or NK cell counts, myelodysplastic syndrome, early stage GATA2 deficiency, availability of specific HLA-matched donors, performance status criteria, left ventricular ejection fraction criteria, adequate organ function criteria, agreement to use contraception, discontinuation of breastfeeding, willingness to remain in or close to the NIH, approval for participants with HBV or HCV, ability to understand and sign informed consent document

Exclusion Criteria

Participants with a Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score >8

Participants who have received investigational agents within 4 weeks before treatment initiation (except virus-specific T cells for viral infection/reactivation)

I do not have a history of blood cancer (except MDS), severe allergies, active cancer (except virus-driven or MDS), HIV, pregnancy, serious illness, or social issues affecting treatment compliance.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Conditioning

Participants receive JSP191 and other medications as part of the conditioning regimen, including total body irradiation

2 weeks

Inpatient stay

Transplantation

Donor stem cells are administered through the central venous catheter

1 day

Inpatient stay

Post-Transplant Monitoring

Participants remain in the hospital and local area for monitoring and receive immunosuppression for GVHD prophylaxis

100 days

Weekly clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• JSP191
• Mycophenolate Mofetil
• Post-Transplant Cyclophosphamide
• Tacrolimus
• Total Body Irradiation

Trial Overview The study tests JSP191's ability to make hematopoietic stem cell transplants safer in GATA2 deficiency patients. It involves screening, conditioning (including JSP191 administration), transplanting donor stem cells, and taking other drugs to prevent side effects. Participants will be closely monitored for three years.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 8 Interventions

Briquilimab, Fludarabine, Cyclophosphamide, Total Body Irradiation

Group II: Arm A Experimental Treatment 7 Interventions

Briquilimab, Fludarabine, Total Body Irradiation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Whole-exome sequencing has significantly improved the identification of genetic defects causing immunodeficiency syndromes, revealing new genes such as PGM3 and CTLA4, which expand our understanding of these conditions.

Newborn screening for T-cell deficiency is being implemented in more states, allowing for early detection and treatment of severe combined immunodeficiency, which is crucial for improving survival rates in affected infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in basic and clinical immunology in 2014. Chinen, J., Notarangelo, LD., Shearer, WT.[2015]

In a study of 11,448 patients at risk for secondary immunodeficiency (SID), those receiving immunoglobulin replacement therapy (IgPro10) experienced significantly fewer infections compared to those who did not receive the treatment.

The IgPro10 group, which included patients with serious conditions like B-cell malignancies and solid organ transplants, showed better infection outcomes despite having more severe health issues at the start of the study, suggesting its effectiveness in preventing infections in SID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced risk of infections with the intravenous immunoglobulin, IgPro10, in patients at risk of secondary immunodeficiency-related infections. Lahue, BJ., Mallick, R., Zhang, X., et al.[2022]

Significant advancements in the treatment of severe combined immunodeficiencies (SCID) have led to successful cures in at least 75% of patients through bone marrow transplantation, whether from HLA identical or non-identical donors.

Emerging therapies, including enzyme substitution for adenosine deaminase (ADA) deficiency and the potential for gene therapy, offer promising alternatives for treating SCID and its various underlying causes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe combined immunodeficiencies. Fischer, A.[2008]

In a study of 28 ADA-deficient patients undergoing 31 HSCT procedures, the overall survival rate was 85.7%, indicating that unconditioned HSCT can be effective, especially with HLA-matched donors.

However, unconditioned procedures showed poorer myeloid engraftment and metabolic correction, leading to a higher need for additional treatments, suggesting that reduced intensity conditioning (RIC) may improve long-term outcomes and should be considered even when a matched donor is available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Immune Recovery After Hematopoietic Stem Cell Transplantation for ADA Deficiency: a Single-Center Experience. Kreins, AY., Velasco, HF., Cheong, KN., et al.[2022]

In a study of 10 SCID patients with various JAK3 mutations, bone marrow transplantation effectively restored T-cell immunity, with all but one patient showing normal T-cell function after the procedure.

However, the restoration of B-cell and NK cell functions was less successful, as only 3 patients regained antibody function and only 2 showed normal NK activity post-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation. Roberts, JL., Lengi, A., Brown, SM., et al.[2022]

Citations

1. ir.jaspertherapeutics.com ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-positive-clinical-data-phase-iii

News Release Details All three sickle cell disease participants treated with briquilimab successfully engrafted with neutrophil engraftment within 12-16 days

2. ir.jaspertherapeutics.com ir.jaspertherapeutics.com/news-releases/news-release-details/jasper-therapeutics-announces-fda-fast-track-designation-jsp191

News Release Details To date, JSP191 has been studied in 14 SCID patients in an ongoing multicenter clinical trial with clinical outcome data presented at academic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636724004949

Pharmacokinetics of Briquilimab as a Conditioning Agent ... Briquilimab, formerly known as AMG 191 or JSP191, is an aglycosylated ... Safety and efficacy data of briquilimab used as the sole HCT-conditioning ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02963064

JSP191 Antibody Targeting Conditioning in SCID Patients A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with SCID undergoing ...

5. ir.jaspertx.com ir.jaspertx.com/news-releases/news-release-details/jasper-therapeutics-announces-updated-data-phase-1-clinical

News Release Details JSP191 is well tolerated with no treatment-related severe adverse events in 24 patients with myelodysplastic syndrome (MDS) or acute myeloid ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05903274

JSP191 (briquilimab) in Subjects with LR-MDS A Phase 1 study in subjects with LR-MDS to assess the safety and tolerability of JSP191 as a second-line therapy. Detailed Description. An open-label, single- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02963064

JSP191 Antibody Targeting Conditioning in SCID Patients A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with SCID undergoing ...