Siplizumab for Sickle Cell Disease Transplant

Conditions

• Anemia, Sickle Cell

Eligibility Criteria

Sex

ALL

Age

18 Years - 50 Years

Healthy Volunteers

Not accepted

Interventions

• Siplizumab — DRUG
  Premedication with diphenhydramine 50 mg PO is to be given 1 hour prior to siplizumab infusion. Premedication with hydrocortisone succinate 100 mg IV infused over 30 minutes and acetaminophen 650 mg PO are to be given at least 30 minutes prior to siplizumab infusion. Siplizumab 4.8 mg/kg total is given on Day -14 and 0.6mg/kg is given on days -6, -1, 0, and +1. It will be given as an IV infusion over 1 hour.
• Exchange Transfusion — PROCEDURE
  Patient will undergo a red blood cell exchange transfusion to achieve a Hemoglobin S (HgbS) level \< 20% prior to starting therapy to prevent the development of a vaso-occlusive Crisis (VOC).
• Total Body Irradiation — PROCEDURE
  Radiation dose is 2Gy (Gy is a radiation unit of measurement). Radiation source and dose rates will be according to institutional practice. Total Body Irradiation (TBI) may be delivered from either linear accelerator or Cobalt sources.
• Stem Cell Infusion — PROCEDURE
  Standard institutional procedures should be followed for the processing and administration of stem cell products for infusion. The infused graft under no circumstances is to be irradiated. No in-line leukocyte filter should be used and no medications or fluids should be given piggyback through the catheter lumen used for infusion of stem cells. Vital signs should be monitored before beginning the infusion and periodically during administration and in accordance with institutional guidelines. Pre-medications prior to the graft infusion will be according to the institutions standard practice. Benadryl, epinephrine, hydrocortisone, and oxygen be available at the bedside, as well as an emergency medical code cart available in the vicinity of the patient, for emergency use in case of an infusion reaction.
• Cyclophosphamide 50mg — DRUG
  Cyclophosphamide will be given on days +3 and +4 at a dose of 50 mg/kg. Hydration prior to cyclophosphamide should be given according to standard institutional practice. Day +3 dose should occur between 60 and 72 hours after graft infusion and day +4 post-transplant should occur approximately 24 hours after prior dose. Cyclophosphamide will be given as an IV infusion over 1-2 hours depending on volume or as per institutional standard practice. Cyclophosphamide will be dosed according to adjusted ideal body weight (AIBW) in patients weighing \> 125% ideal body weight (IBW).
• Mesna — DRUG
  Mesna is to be given starting 1 hour prior to cyclophosphamide at the same dose (50 mg/kg) as a continuous infusion over 24 hours.
• Sirolimus Oral Tablet — DRUG
  Sirolimus will be given orally with a loading dose of 12 mg, then followed by 4 mg orally daily. Dosage will be adjusted to a therapeutic target of 10 - 15ng/ml in first 3 months post transplant and 3-10 after 3 months. Sirolimus should be started on day +5. It will be continued until at least day 180. Sirolimus can be tapered or continued according to the treating physician discretion and the presence of absence of GVHD and/or degree of donor chimerism. Sirolimus should be continued if donor chimerism is less than 50% to prevent graft loss.
• Rituximab or Biosimilar — DRUG
  Rituximab (375 mg/m2/dose) will be administered on Days -14 and -6. In those subjects receiving ongoing renal replacement therapy, rituximab should be administered several hours after hemodialysis. The first rituximab solution for infusion should be administered intravenously at an initial rate of 50 milligrams/hour (mg/hr). The rate may be escalated by 50mg/hr every 30 minutes to a maximum of 400 mg/hr. Subsequent infusions may be started at 100 milligrams/hour (mg/hr) and titrated by 100 mg/hr every 30 minutes to a maximum of 400mg/hr if the subject tolerated the first infusion.

Study Details

The purpose of this study is to find out whether siplizumab is safe and effective for patients with SCD undergoing an allogeneic transplant and to prevent development of Graft versus Host Disease (GVHD) and graft failure. The main goals of this study are : * To determine if acute GVHD occurs and how severe the acute GVHD is in subjects receiving the study drug * To determine if graft failure occurs in subjects receiving the study drugs In this study, participants will receive 5 infusions of the study drug, siplizumab, while getting a stem cell transplant for SCD. Before siplizumab infusion, participants will be given medications to reduce the risks of allergic reaction to the drug.

Key Dates

Start date

Sep 28, 2023

Status verified

Jun 2026

Primary completion

Dec 11, 2024

Completion

Dec 11, 2025

Study Design

Enrollment

1 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Siplizumab
  Participants will receive 5 infusions of siplizumab. The first dose is given 14 days prior to the infusion of stem cells; the second dose is given 6 days before infusion; and doses 3, 4, and 5 are given on the day before, day of, and day after stem cell infusion.

Primary Outcome Measure

Failure Rate [ Time Frame: 12 Months Post Stem Cell Transplant ]

Locations (1)

Find similar trials in New York, NY

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