Siplizumab for Sickle Cell Disease Transplant

NCT06078696 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAU5053
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anemia, Sickle Cell

Keywords

hemoglobin S (HbS) Disease; Hemoglobin S Disease; Sickle Cell Disease; Sickle Cell Disorders; Sickling Disorder Due to Hemoglobin S; Advanced Sickle Cell Disease; Sβ0 thalassemia; Advanced SCD

Outcome Measures

Primary Outcomes (1)

• Failure Rate

  Failure rate is a safety endpoint. Failure rate is defined as: graft failure (Primary Graft Rejection: Primary graft rejection is defined as the absence of donor cells (% donor cells \< 5%) assessed by bone marrow or peripheral blood chimerism assays by Day 42. Late Graft Rejection: The absence (\<5%) of donor hematopoietic cells in peripheral blood or bone marrow beyond Day 42 in a patient who had initial evidence of hematopoietic recovery with \> 20% donor cells will be considered a late graft rejection.); or grades III-IV GVHD (as assessed by Center for International Blood and Marrow Transplant Research (CIBMTR) and NIH Consensus Criteria); or death at 100 days.

  12 Months Post Stem Cell Transplant

Secondary Outcomes (6)

• Time to Engraftment

  Day 100

• Incidence of GVHD of Any Grade

  12 Months Post Stem Cell Transplant

• Incidence of Other Transplant Related Toxicities

  12 Months Post Stem Cell Transplant

• Incidence of Significant Transplant-related Infections

  12 Months Post Stem Cell Transplant

• Number of Participants With Donor Chimerism >5%

  Day 30, Day 100, and 1 year

Study Arms (1)

Siplizumab

EXPERIMENTAL

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.

Drug: Siplizumab; Procedure: Exchange Transfusion; Procedure: Total Body Irradiation; Procedure: Stem Cell Infusion; Drug: Cyclophosphamide 50mg; Drug: Mesna; Drug: Sirolimus Oral Tablet; Drug: Rituximab or Biosimilar

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.

Also known as: TCD601 (Siplizumab)

Siplizumab

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).

Siplizumab

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.

Also known as: TBI

Siplizumab

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.

Siplizumab

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).

Also known as: Cytoxan, Cytoxan Lyophilized

Siplizumab

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.

Also known as: Mesnex

Siplizumab

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.

Also known as: Rapamycin, Rapamune

Siplizumab

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.

Also known as: Riabni, Rituxan, Ruxience, Truxima

Siplizumab

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients with sickle cell anemia (Hb SS, Sβ0 thalassemia or severe SC) who are 18 - 50 years of age inclusive AND who have 1 or more of the following:
• Clinically significant neurologic event (stroke) or any neurological deficit lasting at least 24 hours. Stroke will be defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy.
• History of two or more episodes of ACS in the 2-year period preceding enrollment despite supportive care measures (i.e. asthma therapy and/or hydroxyurea).
• History of three or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
• Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year for 1 year or more to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and ACS)
• An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity \> or equal to 2.7 m/sec or pulmonary hypertension diagnosed by right heart catheterization.
• Chronic kidney disease including patients on hemo-dialysis
• Recurrent tricorporal priapism defined as at least 2 episodes of an erection last ≥4 hours involving the corpus cavernosa and corpus spongiosa.
• Recipient cannot be pregnant or lactating.
• Adequate organ functions as defined as:
• Eastern Cooperative Group (ECOG) performance status of 2 or better
• Cardiac function: left ventricular ejection fraction (LVEF) of 40% or greater
• Pulmonary Function: Pulse oximetry with a baseline oxygen saturation of 85% or greater and corrected diffusing capacity of the Lungs for carbon monoxide (DLCO) of 35% or greater
• Hepatic Function: Serum conjugated (direct) bilirubin less than 3x upper limit of normal for age as per local laboratory, alanine aminotransferase (ALT) and aspartate transaminase (AST) less than 5 x upper limit of normal as per local laboratory. Patients whose hyperbilirubinemia is the result of hyperhaemolysis, or a sever drop in hemoglobin post blood transfusion are not excluded.
• Absence of liver cirrhosis, bridging fibrosis and active hepatitis as documented by liver biopsy for patients with evidence of iron overload by serum ferritin or MRI. The histological grading and scale described by Ishak and colleagues (1995) will be used.

You may not qualify if:

• Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 35% of predicted OR baseline oxygen saturation of \<85% or oxygen pressure in arterial blood (PaO2) \<70.
• Liver iron content (LIC) ≥15 mg Fe/g dry weight on R2 MRI of liver, unless liver biopsy within 3 months prior to or at screening shows no evidence of bridging fibrosis or cirrhosis. Presence of bridging (portal to portal) fibrosis or cirrhosis in liver biopsy OR transaminases \>5x normal upper limit (ULN) for age or direct bilirubin \>3x normal upper limit (ULN).
• Clinical stroke within 6 months of anticipated transplant
• Karnofsky performance score \< 50%
• HIV infection
• Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment.
• Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT in the opinion of the investigator.
• Patient unable to understand the nature and risks inherent in the HSCT process.
• History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation.
• Patient is pregnant or lactating.
• Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor.
• Presence of donor-specific HLA antibodies
• Donor Eligibility and Selection Criteria
• Please note, donor selection will follow our institutional standard operating procedure (SOP). Key criteria are summarized below for convenience:
• Donor should be evaluated for eligibility to donate by an independent physician not directly caring for the patient on study protocol

Sponsors & Collaborators

• Columbia University: lead
• ITB-Med LLC: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Anemia, Sickle Cell; Sickle Cell Trait; Disease

Interventions

siplizumab; Exchange Transfusion, Whole Blood; Whole-Body Irradiation; Cyclophosphamide; Mesna; Sirolimus; Rituximab; Biosimilar Pharmaceuticals

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Blood Transfusion; Biological Therapy; Therapeutics; Radiotherapy; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Macrolides; Lactones; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Markus Y. Mapara, MD, Professor of Medicine
• Organization: Columbia University

mym2111@cumc.columbia.edu

212-342-0530

Study Officials

• Markus Y Mapara, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2023
• First Posted: October 12, 2023
• Study Start: September 28, 2023
• Primary Completion: December 11, 2024
• Study Completion: December 11, 2025
• Last Updated: February 27, 2026
• Results First Posted: February 27, 2026

Record last verified: 2026-02

Locations

US (1)