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Closed by the industry collaborator
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| Name | Class |
|---|---|
| ITB-Med LLC | INDUSTRY |
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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 :
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.
Phase I/II label single arm safety assessment study of Siplizumab-based conditioning. It is designed to determine the safety and feasibility of hematopoietic stem cell transplantation for patients with advanced sickle cell disease using in vivo T cell depletion with Siplizumab.
It is a three-stage design with a target sample size of at most 18 patients. At the first stage, a total of 6 patients will be recruited, the study will be stopped, if 2 or more of patients experience any of the following events: graft failure/Grade 3-4 acute GVHD/death in the first 100 days. If not, the study will proceed to the second stage and recruit additional 6 patients. The study will be stopped if 4 or more patients experience an event as specified above among the 12 patients. If not, the study will proceed to the third stage and recruit additional 6 patients, the study will be stopped any time if 6 or more patients experience an event among the 18 patients. The study will be stopped at any time if a patient death occurs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Engraftment | Time to neutrophil engraftment is defined as the first of 3 measurements on consecutive days when the patient has an absolute neutrophil count of 500/μL after conditioning. Time to platelet engraftment will be defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count > 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. Time to red cell engraftment is defined as the first of two measurements on different days that the patient has achieved an absolute reticulocyte count > 30,000/μL following conditioning regimen induced nadir. |
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Recipient Inclusion Criteria:
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:
Adequate organ functions as defined as:
Patient must have a matched-or mismatched unrelated donor or mismatched related family donor.
Recipient Exclusion Criteria:
Donor Eligibility and Selection Criteria
Please note, donor selection will follow our institutional standard operating procedure (SOP). Key criteria are summarized below for convenience:
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| Name | Affiliation | Role |
|---|---|---|
| Markus Y Mapara, MD, PhD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Irving Medical Center | New York | New York | 10032 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1).
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | 12 Months Post Stem Cell Transplant |
|
2 years
Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Markus Y. Mapara, MD, Professor of Medicine | Columbia University | 212-342-0530 | mym2111@cumc.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 19, 2023 | Feb 9, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D012805 | Sickle Cell Trait |
| D004194 | Disease |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
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| ID | Term |
|---|---|
| C544394 | siplizumab |
| D005078 | Exchange Transfusion, Whole Blood |
| D014916 | Whole-Body Irradiation |
| D003520 | Cyclophosphamide |
| D015080 | Mesna |
| D020123 | Sirolimus |
| D000069283 | Rituximab |
| D059451 | Biosimilar Pharmaceuticals |
| ID | Term |
|---|---|
| D001803 | Blood Transfusion |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D011878 | Radiotherapy |
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|
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| 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. |
|
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| 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. |
|
|
| Day 100 |
| Incidence of GVHD of Any Grade | Incidence of acute and chronic GVHD of any grade as evaluated according to the CIBMTR and NIH criteria respectively. | 12 Months Post Stem Cell Transplant |
| Incidence of Other Transplant Related Toxicities | Incidence of other transplant related toxicities, including Veno-occlusive disease (VOD), Idiopathic pneumonia syndrome (IPS), Central nervous system (CNS) toxicity, or Posterior reversible encephalopathy syndrome (PRES). | 12 Months Post Stem Cell Transplant |
| Incidence of Significant Transplant-related Infections | Significant infections will be recorded including but not limited to bacterial or fungal sepsis, cytomegalovirus (CMV) reactivation with/without clinical disease, adenovirus infection, epstein-barr virus (EBV) reactivation with or without post-transplant lymphoproliferative disorders (PTLD), other significant viral reactivations or community-acquired viral infections and invasive mold infections. | 12 Months Post Stem Cell Transplant |
| Number of Participants With Donor Chimerism >5% | Chimerism is a measure of the engraftment of donor cells within the recipient and is expressed as the percentage ratio between the number of donor cells and recipient cells. Chimerism will be determined by Short Tandem Repeat analysis. | Day 30, Day 100, and 1 year |
| Percentage of Participants Who Achieve Immune Reconstitution | Peripheral blood quantitative assessment of the main lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, and CD16+/56+). Lymphocytes will be assessed by flow cytometry. In addition, quantitative immunoglobulins will be measured for Immunoglobulin A (IgA), Immunoglobulin M (IgM) and Immunoglobulin (IgG). These will be performed at Day +60 (±10 days) as well as at 1 year (+/- 2 weeks) and after long term follow up at the discretion of the investigator. Descriptive statistics will be used to describe the percentage of patient who are able to achieve reconstitution of important lymphocyte subsets and B cell function at the defined timepoint above. | 12 Months Post Stem Cell Transplant |
|
| Sex: Female, Male |
|
| Ethnicity (NIH/OMB) |
|
| Race (NIH/OMB) |
|
| Region of Enrollment | participants |
|
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.
|
| Secondary | Time to Engraftment | Time to neutrophil engraftment is defined as the first of 3 measurements on consecutive days when the patient has an absolute neutrophil count of 500/μL after conditioning. Time to platelet engraftment will be defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count > 50,000/μL AND did not receive a platelet transfusion in the previous 7 days. Time to red cell engraftment is defined as the first of two measurements on different days that the patient has achieved an absolute reticulocyte count > 30,000/μL following conditioning regimen induced nadir. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | Day 100 |
|
|
| Secondary | Incidence of GVHD of Any Grade | Incidence of acute and chronic GVHD of any grade as evaluated according to the CIBMTR and NIH criteria respectively. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | 12 Months Post Stem Cell Transplant |
|
|
| Secondary | Incidence of Other Transplant Related Toxicities | Incidence of other transplant related toxicities, including Veno-occlusive disease (VOD), Idiopathic pneumonia syndrome (IPS), Central nervous system (CNS) toxicity, or Posterior reversible encephalopathy syndrome (PRES). | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | 12 Months Post Stem Cell Transplant |
|
|
| Secondary | Incidence of Significant Transplant-related Infections | Significant infections will be recorded including but not limited to bacterial or fungal sepsis, cytomegalovirus (CMV) reactivation with/without clinical disease, adenovirus infection, epstein-barr virus (EBV) reactivation with or without post-transplant lymphoproliferative disorders (PTLD), other significant viral reactivations or community-acquired viral infections and invasive mold infections. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | 12 Months Post Stem Cell Transplant |
|
|
| Secondary | Number of Participants With Donor Chimerism >5% | Chimerism is a measure of the engraftment of donor cells within the recipient and is expressed as the percentage ratio between the number of donor cells and recipient cells. Chimerism will be determined by Short Tandem Repeat analysis. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | Day 30, Day 100, and 1 year |
|
|
| Secondary | Percentage of Participants Who Achieve Immune Reconstitution | Peripheral blood quantitative assessment of the main lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, and CD16+/56+). Lymphocytes will be assessed by flow cytometry. In addition, quantitative immunoglobulins will be measured for Immunoglobulin A (IgA), Immunoglobulin M (IgM) and Immunoglobulin (IgG). These will be performed at Day +60 (±10 days) as well as at 1 year (+/- 2 weeks) and after long term follow up at the discretion of the investigator. Descriptive statistics will be used to describe the percentage of patient who are able to achieve reconstitution of important lymphocyte subsets and B cell function at the defined timepoint above. | Data was not analyzed or disclosed in an effort to protect participant confidentiality (n=1). Additionally, since there is only one participant, it is not possible to report summary level data. | Posted | 12 Months Post Stem Cell Transplant |
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| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
| 0 |
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| D006425 |
| Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008919 |
| Investigative Techniques |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D018942 | Macrolides |
| D007783 | Lactones |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |