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

Conditions

• Sickle Cell Disease

Eligibility Criteria

Sex

ALL

Age

2 Years - 25 Years

Healthy Volunteers

Not accepted

Interventions

• Daratumumab — DRUG
  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.
• Alemtuzumab — DRUG
  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.
• Sirolimus — DRUG
  Sirolimus is an mTOR inhibitor immunosuppressant used to prevent organ transplant rejections as well as treat lymphangioleiomyomatosis and adults with perivascular epithelioid cell tumors.
• Total Body Irradiation — RADIATION
  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.

Study Details

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.

Key Dates

Start date

Apr 3, 2024

Status verified

Sep 2025

Primary completion

Sep 30, 2044

Completion

Sep 30, 2054

Study Design

Enrollment

12 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Recipients with a major ABO incompatible donor
  Patients in this cohort are treated pre-HCT with Daratumumab, intravenously, on days -49, -42, -35 and -28. The conditioning regimen will consist of alemtuzumab, given subcutaneously, daily for 5 days (days -7 to -3) and low dose total body irradiation (TBI) 300 cGY on day -2 with gonadal shielding. Sirolimus will be given as GVHD prophylaxis for the first year with weaning thereafter based on donor T-cell chimerism. G-CSF, at 5 mcg/kg/day, will be given post stem cell infusion until neutrophil engraftment is achieved.
• Experimental: Recipients with red cell alloantibodies (non-ABO) against donor antigens
  Patients in this cohort are treated pre-HCT with Daratumumab, intravenously, on days -49, -42, -35 and -28. The conditioning regimen will consist of alemtuzumab, given subcutaneously, daily for 5 days (days -7 to -3) and low dose total body irradiation (TBI) 300 cGY on day -2 with gonadal shielding. Sirolimus will be given as GVHD prophylaxis for the first year with weaning thereafter based on donor T-cell chimerism. G-CSF, at 5 mcg/kg/day, will be given post stem cell infusion until neutrophil engraftment is achieved.

Primary Outcome Measure

To determine the event-free survival of children and adolescents with SCD undergoing nonmyeloablative HCT who received 4 doses of pre-HCT daratumumab for donor-directed red blood cell antibodies. [ Time Frame: 1-year post-transplant ]

Central Contacts

• Robert Nickel, MD
  202-476-3122
  [email protected]
• Maryanne Odinakachukwu
  202-476-2957
  [email protected]

Locations (1)

Find similar trials in Washington D.C., DC

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