Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia

Summary

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.

Conditions

• Sickle Cell Anemia
• Beta Thalassemia

Interventions

DRUG

Filgrastim (G-CSF)

May be used to minimize the days of neutropenia, and may be administered beginning near day 10 post stem cell infusion at 5 mcg/kg (rounding to the nearest vial) at the discretion of investigator.

RADIATION

TBI

300 cGy total body irradiation (TBI, day -2)

DRUG

Hydroxyurea

Optimized 4-12 weeks prior to planned transplant date

BIOLOGICAL

briquilimab

briquilimab, anti-CD117 monoclonal antibody at 0.6mg/kg at day -11 prior to infusion of allogeneic HSCs

DRUG

Sirolimus

For immune suppression (day -1)

BIOLOGICAL

Alemtuzumab

Alemtuzumab 1 mg/kg of alemtuzumab divided over 5 days (-7 through -3),

DRUG

Plerixafor

For autologous HSC collection; dose of plerixafor at 240 mcg/kg (capped at 20mg)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• John F Tisdale, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

4 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-05-12

Primary Completion

2026-01-31

Completion

2027-01-31

FDA Drug

Yes

Countries

• United States

Study Locations