Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell Antibody

Summary

This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.

Conditions

• Sickle Cell Disease

Interventions

DRUG

Daratumumab

Daratumumab is a cytotoxic monoclonal antibody (IgG1k) to CD38 and is commercially approved to treat multiple myeloma. CD38 is expressed on several types of blood cells including B-cells, antibody-secreting plasma blasts and plasma cells. As a result, it has been used to treat antibody-mediated diseases, including children with antibody-mediated cytopenias post-HCT.

DRUG

Alemtuzumab

Alemtuzumab is a humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein, CD52.

DRUG

Sirolimus

Sirolimus is an mTOR inhibitor immunosuppressant used to prevent organ transplant rejections as well as treat lymphangioleiomyomatosis and adults with perivascular epithelioid cell tumors.

RADIATION

Total Body Irradiation

Total body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. The radiation is given in a low dose so that normal tissues can repair themselves.

Sponsors & Collaborators

• Alberta Children's Hospital

  collaborator OTHER

• The Hospital for Sick Children

  collaborator OTHER

• Levine Children's Hospital

  collaborator OTHER

• Ann & Robert H Lurie Children's Hospital of Chicago

  collaborator OTHER

• Nationwide Children's Hospital

  collaborator OTHER

• Children's Hospital at Montefiore

  collaborator OTHER

• Doris Duke Charitable Foundation

  collaborator OTHER

• Janssen Pharmaceuticals

  collaborator INDUSTRY

• Children's National Research Institute

  lead OTHER

Principal Investigators

• Robert Nickel, MD · Children's National Research Institute

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-04-03

Primary Completion

2044-09-30

Completion

2054-09-30

FDA Drug

Yes

Countries

• United States

Study Locations