JSP191 + Stem Cell Transplant for Sickle Cell Anemia

Overseen By Kelly S Norris

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: ECOG status, DLCO, Oxygen saturation, others

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

Compensation: Varies

Number of Visits: 3

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: Sickle cell disease (SCD) is an inherited disorder of the blood. It can damage a person s organs and cause serious illness and death. A blood stem cell transplant is the only potential cure for SCD. Treatments that improve survival rates are needed. Objective: To find out if a new antibody drug (briquilimab, JSP191) improves the success of a blood stem cell transplant Eligibility: People aged 13 or older who are eligible for a blood stem cell transplant to treat SCD. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood. Design: Participants receiving transplants will undergo screening. They will have blood drawn. They will have tests of their breathing and heart function. They may have chest x-rays. A sample of marrow will be collected from a pelvic bone. Participants will remain in the hospital about 30 days for the transplant and recovery. They will have a large intravenous line inserted into the upper arm or chest. The line will remain in place for the entire transplant and recovery period. The line will be used to draw blood as needed. It will also be used to administer the transplant stem cells as well as various drugs and blood transfusions. Participants will also receive some drugs by mouth. Participants must remain within 1 hour of the NIH for 3 months after transplant. During that time, they will visit the clinic up to 2 times a week. Follow-up visits will include tests to evaluate participants mental functions. They will have MRI scans of their brain and heart.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. However, it mentions that participants with certain complications must be on sickle cell treatment/medication, suggesting that some medications may need to be continued.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the trial involves a stem cell transplant, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

How is the JSP191 + Stem Cell Transplant treatment different from other treatments for sickle cell anemia?

The JSP191 + Stem Cell Transplant treatment is unique because it combines a novel antibody (JSP191) with a stem cell transplant, potentially offering a less toxic alternative to traditional chemotherapy-based conditioning regimens. This approach aims to improve engraftment and reduce complications associated with sickle cell anemia treatments. ^{1 2 3 4 5}

How is the JSP191 treatment for sickle cell anemia different from other treatments?

JSP191 combined with stem cell transplant is unique because it uses a targeted approach to prepare the body for the transplant, potentially reducing the risk of complications like graft-versus-host disease (a condition where the donor cells attack the recipient's body) and improving the chances of successful engraftment compared to traditional methods that use more intense chemotherapy or radiation. ^{1 2 3 4 5}

Research Team

John F Tisdale, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is for people aged 13 or older with sickle cell disease (SCD) at high risk due to organ damage or complications, and those with beta-thalassemia who have significant iron overload. Participants must be eligible for a blood stem cell transplant and have a matched family donor. They should understand the study procedures, agree to use birth control during the study, and not be pregnant or breastfeeding.

Inclusion Criteria

I am at least 4 years old, weigh 20 kg or more, and willing to donate stem cells and blood for research.

I have beta-thalassemia with moderate to severe iron overload.

Negative serum or urine beta-HCG

Exclusion Criteria

Baseline oxygen saturation of <85% or PaO2 <70

Evidence of uncontrolled bacterial, viral, or fungal infections within one month prior to starting the conditioning regimen

Left ventricular ejection fraction: <35% estimated by ECHO

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Transplant and Recovery

Participants remain in the hospital for the transplant and recovery, receiving stem cells and various drugs

4 weeks

Inpatient stay

Post-Transplant Monitoring

Participants must remain within 1 hour of the NIH for 3 months post-transplant, with clinic visits up to 2 times a week

12 weeks

Up to 2 visits per week (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mental function tests and MRI scans

1 year

Regular follow-up visits

Treatment Details

Interventions

• Alemtuzumab
• Filgrastim (G-CSF)
• Hydroxyurea
• JSP191
• Plerixafor
• Sirolimus
• TBI

Trial Overview The trial tests whether adding briquilimab (JSP191), an antibody drug, improves outcomes of nonmyeloablative hematopoietic cell transplantation in treating SCD and beta-thalassemia. It involves hospitalization for about 30 days for the transplant procedure followed by close monitoring up to three months post-transplant.

Participant Groups

Group I: briquilimab in stem cell transplant recipients for SCD Experimental Treatment 7 Interventions

Affected SCD and beta-thal subjects will receive briquilimab

Group II: Stem cell Donors of Recipients undergoing stem cell transplant Active Control 1 Intervention

Participants donate stem cells for recipient to undergo stem cell transplant

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Findings from Research

In a study involving 13 high-risk adult patients with sickle cell disease, a chemotherapy-free stem cell transplantation regimen resulted in successful engraftment in all patients, with 92% maintaining stable mixed donor/recipient chimerism after a median follow-up of 22 months.

The treatment showed no mortality or graft-versus-host disease, and patients experienced significant improvements in hemoglobin levels and quality of life, including aspects like bodily pain and vitality, highlighting the efficacy and safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2017]

Targeted marrow irradiation (TMI) at a dose of 8 Gy to the bone marrow and 2 Gy to the rest of the body shows promise as a safer alternative to traditional total body irradiation (TBI) for hematopoietic stem cell transplant in sickle cell disease, resulting in reduced organ damage and better donor cell engraftment.

In a preclinical study using a sickle cell mouse model, TMI led to successful long-term engraftment and significant recovery of sickle cell disease features, including improved red blood cell counts and vascular health, indicating its potential efficacy in treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease. Sargur Madabushi, S., Fouda, R., Ghimire, H., et al.[2022]

A multicenter pilot study involving 22 adults with severe sickle cell disease demonstrated that a reduced toxicity bone marrow transplantation (BMT) regimen is feasible and safe, achieving a 1-year overall survival rate of 91% and an event-free survival rate of 86%.

The study showed significant improvements in health-related quality of life, particularly in pain interference and physical function, indicating that BMT can enhance the quality of life for patients with severe sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Krishnamurti, L., Neuberg, DS., Sullivan, KM., et al.[2020]

In a study of 50 adult patients with sickle cell disease referred for haploidentical hematopoietic stem cell transplantation (HSCT), only 10 patients underwent the procedure, highlighting challenges such as insurance denial and patient reluctance.

The modified Hopkins regimen used for HSCT resulted in a high engraftment rate of 87.5% and low morbidity, with 87.5% of patients alive at a median follow-up of 16 months, suggesting its potential for broader application in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease. Saraf, SL., Oh, AL., Patel, PR., et al.[2023]

A Phase II clinical trial of haploidentical bone marrow transplantation (BMT) with post-transplantation cyclophosphamide showed a 93% stable donor engraftment rate at 6 months and 100% overall survival among 15 patients, indicating high efficacy for treating severe sickle cell disease (SCD).

The addition of thiotepa to the conditioning regimen reduced the risk of graft rejection, with only 2 patients experiencing severe acute graft-versus-host disease (GVHD), suggesting that this approach minimizes transplantation-related morbidity while improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative. de la Fuente, J., Dhedin, N., Koyama, T., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease. [2017]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Development and characterization of a preclinical total marrow irradiation conditioning-based bone marrow transplant model for sickle cell disease. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Haploidentical Peripheral Blood Stem Cell Transplantation Demonstrates Stable Engraftment in Adults with Sickle Cell Disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative. [2020]