RECRUITING

Siplizumab for Sickle Cell Disease Transplant

Conditions

Anemia, Sickle Cell 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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Siplizumab-based Conditioning for Hematopoietic Stem Cell Transplantation in Patients With Advanced Sickle Cell Disease (CD2 SCD)

Quick Facts

Study Start:2023-09-28

Study Completion:2029-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06078696

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
1. 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: 1. 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. 2. 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). 3. 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). 4. 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) 5. 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. 6. Chronic kidney disease including patients on hemo-dialysis 7. Recurrent tricorporal priapism defined as at least 2 episodes of an erection last ≥4 hours involving the corpus cavernosa and corpus spongiosa. 8. Recipient cannot be pregnant or lactating. 2. Adequate organ functions as defined as: 1. Eastern Cooperative Group (ECOG) performance status of 2 or better 2. Cardiac function: left ventricular ejection fraction (LVEF) of 40% or greater 3. 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 4. 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. 5. 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. 3. Patient must have a matched-or mismatched unrelated donor or mismatched related family donor. 1. For HLA-matching we will assess 12 HLA-antigens (HLA-A, B, C, DRB1, DQB1 and DPB1). 2. Fully matched unrelated transplanted are defined as matched at 12/12 HLA-alleles. We will include up to 7/8 (HLA-A, B, C, and DRB1) matched unrelated donors. 3. One haplotype-mismatched related donors will be included.	1. 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. 2. Severe cardiac dysfunction defined as ejection fraction \<45% or subjects who have been receiving chronic transfusion therapy for \> 1 year and have evidence of iron overload (serum ferritin levels \>1000 ng/mL), a cardiac MRI is required. Cardiac T2\* \<10 ms results in exclusion. 3. 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). 4. Clinical stroke within 6 months of anticipated transplant 5. Karnofsky performance score \< 50% 6. HIV infection 7. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment. 8. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT in the opinion of the investigator. 9. Patient unable to understand the nature and risks inherent in the HSCT process. 10. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation. 11. Patient is pregnant or lactating. 12. Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor. 13. Presence of donor-specific HLA antibodies 1. Donor should be evaluated for eligibility to donate by an independent physician not directly caring for the patient on study protocol 2. Donor is willing to sign informed consent allowing the use of the peripheral blood stem cell (PBSC) product for the hematopoietic stem cell transplant (HSCT) of the recipient 3. Donor must meet HLA match criteria outlined in the inclusion criteria above 4. Donor cannot be pregnant or lactating and must agree to contraception until after the donation procedure is complete 5. Testing negative for HIV and viral hepatitis 6. Free of Hb S (defined as Hb S less than 50%) and other hemoglobinopathies that are symptomatic or of clinical significance 7. Targeted minimum stem cell dose of 5.0 x 10e6 CD34 cells/Kg (a marker of human hematopoietic stem cells) of recipient weight 8. Fulfills standard criteria for eligibility as a donor for hematopoietic stem cell transplant (HSCT)

Inclusion Criteria

Exclusion Criteria

1. 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:
1. 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.
2. 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).
3. 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).
4. 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)
5. 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.
6. Chronic kidney disease including patients on hemo-dialysis
7. Recurrent tricorporal priapism defined as at least 2 episodes of an erection last ≥4 hours involving the corpus cavernosa and corpus spongiosa.
8. Recipient cannot be pregnant or lactating.
2. Adequate organ functions as defined as:
1. Eastern Cooperative Group (ECOG) performance status of 2 or better
2. Cardiac function: left ventricular ejection fraction (LVEF) of 40% or greater
3. 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
4. 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.
5. 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.
3. Patient must have a matched-or mismatched unrelated donor or mismatched related family donor.
1. For HLA-matching we will assess 12 HLA-antigens (HLA-A, B, C, DRB1, DQB1 and DPB1).
2. Fully matched unrelated transplanted are defined as matched at 12/12 HLA-alleles. We will include up to 7/8 (HLA-A, B, C, and DRB1) matched unrelated donors.
3. One haplotype-mismatched related donors will be included.

1. 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.
2. Severe cardiac dysfunction defined as ejection fraction \<45% or subjects who have been receiving chronic transfusion therapy for \> 1 year and have evidence of iron overload (serum ferritin levels \>1000 ng/mL), a cardiac MRI is required. Cardiac T2\* \<10 ms results in exclusion.
3. 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).
4. Clinical stroke within 6 months of anticipated transplant
5. Karnofsky performance score \< 50%
6. HIV infection
7. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment.
8. Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT in the opinion of the investigator.
9. Patient unable to understand the nature and risks inherent in the HSCT process.
10. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation.
11. Patient is pregnant or lactating.
12. Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor.
13. Presence of donor-specific HLA antibodies
1. Donor should be evaluated for eligibility to donate by an independent physician not directly caring for the patient on study protocol
2. Donor is willing to sign informed consent allowing the use of the peripheral blood stem cell (PBSC) product for the hematopoietic stem cell transplant (HSCT) of the recipient
3. Donor must meet HLA match criteria outlined in the inclusion criteria above
4. Donor cannot be pregnant or lactating and must agree to contraception until after the donation procedure is complete
5. Testing negative for HIV and viral hepatitis
6. Free of Hb S (defined as Hb S less than 50%) and other hemoglobinopathies that are symptomatic or of clinical significance
7. Targeted minimum stem cell dose of 5.0 x 10e6 CD34 cells/Kg (a marker of human hematopoietic stem cells) of recipient weight 8. Fulfills standard criteria for eligibility as a donor for hematopoietic stem cell transplant (HSCT)

Contacts and Locations

Study Contact

Research Nurse Navigator

CONTACT

(212) 342 5162

cancerclinicaltrials@cumc.columbia.edu

Markus Y. Mapara

CONTACT

212-342-0530

mym2111@cumc.columbia.edu

Principal Investigator

Markus Y Mapara, MD, PhD

PRINCIPAL_INVESTIGATOR

Columbia University

Study Locations (Sites)

Columbia University Irving Medical Center

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Markus Mapara

Markus Y Mapara, MD, PhD, PRINCIPAL_INVESTIGATOR, Columbia University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-28

Study Completion Date2029-07

Study Record Updates

Study Start Date2023-09-28

Study Completion Date2029-07

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Anemia, Sickle Cell