Non-myeloablative Haploidentical HCT Study for Patients With Sickle Cell Disease, Including Compromised Organ Function

Summary

Background:

Sickle cell disease (SCD) is a genetic disorder where red blood cells, that carry oxygen, are stiff and become stuck in small blood vessels. As a result, affected patients can experience severe pain and serious organ damage. SCD can be cured with a hematopoietic cell transplant (HCT), that is, when they receive blood stem cells from a family donor. But HCT can also have serious side effects, especially in people with organ damage. Researchers want to find ways to make HCT safer for everyone.

Objective:

To test a new combination of drugs (briquilimab, abatacept, and alemtuzumab), used along with radiation, in people undergoing HCT for SCD.

Eligibility:

People aged 16 and older with SCD. They must be eligible for HCT and have a family member who is a good donor match. Donors must be aged 4 and older.

Design:

Participants with SCD will be screened. They will have blood tests and tests of organs including their heart and lung function. Donors will have blood drawn.

Participants with SCD will have a tube inserted into a blood vessel in their chest (intravenously). This line will remain in place up to 2 months; it will be used to draw blood and administer the donor cells and other medications.

Briquilimab will be administered intravenously 1 time, along with other drugs used to prepare for HCT. Participants will receive abatacept 6 times, from just before they receive their donor cells until 6 months after. Participants will undergo radiation therapy and take other drugs that are standard for HCT. Most HCT recipients remain in the hospital for about 30 days after HCT.

Follow-up visits will continue for 5 years....

Conditions

• Sickle Cell Disease

Interventions

BIOLOGICAL

Briquilimab

All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.

DRUG

Filgrastim

A haploidentical relative donor will receive filgrastim (G-CSF) 10 to 16 µg/kg/d subcutaneously or intravenously for up to 6 days with apheresis collections of peripheral blood hematopoietic progenitor cells (PBPC) after the 5th day (and after the 6th day if required).

DRUG

Abatacept

All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.

DRUG

Sirolimus

All stem cell recipient participants will receive the same dose of the investigational briquilimab antibody and abatacept added to the NIH-established regimen of alemtuzumab-TBI-sirolimus and infusion of filgrastim-mobilized peripheral blood hematopoietic cells from haploidentical related donors.

DRUG

Cyclophosphamide

For cohort 1, stem cell recipient participants will receive a single dose of PT-Cy; 50 mg/kg, on day +3 post-HCT. For cohort 2, stem cell participants will receive two doses of PT-Cy; 50mg/kg, on days +3 and +4 (total 100 mg/kg) post-HCT.

Sponsors & Collaborators

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

  lead NIH

Principal Investigators

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

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

4 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-12-28

Primary Completion

2025-10-27

Completion

2027-11-26

FDA Drug

Yes

Countries

• United States

Study Locations