RECRUITING

131I-apamistamab-based Conditioning for Hematopoietic Stem Cell Transplant (HSCT) in Advanced Sickle Cell Disease (SCD)

Conditions

Sickling Disorder Due to Hemoglobin S severe sickle cell disease severe SCD sickle cell disease sickle cell advanced SCD advanced sickle cell disease anemia sickle cell disorders hemoglobin S (HbS) Disease Hemoglobin S Disease

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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 the smallest amount of the 131 I-apamistamab needed for preparing patients with severe sickle cell disease (SCD) for a bone marrow transplant. This is the first time 131 I-apamistamab is being used for advanced Sickle Cell Disease (SCD) in the setting of allogeneic stem cell transplant. 131 I-apamistamab is an investigational product. This means that 131 I-apamistamab has not been approved by the Food and Drug Administration (FDA) for medical use in patients. The study treatment that is given before the transplant is called the conditioning regimen. In this study, the investigators are adding a drug called 131 I-apamistamab instead of the conditioning regimen typically given before a stem cell transplant.

Official Title

Open-label, Single-Center, Phase 1 Study to Estimate the Minimum Effective Dose (MED) of 131I-apamistamab for Non-myeloablative Conditioning in Patients With Severe Sickle Cell Disease

Quick Facts

Study Start:2025-04-28

Study Completion:2032-03-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT07015684

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:12 Years to 50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Availability of an HLA-matched sibling donor * Patients with sickle cell anemia (Hb SS, Sβ0 thalassemia or severe SC) who are 12 - 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 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 catherization. 6. Sickle hepatopathy defined as EITHER ferritin \>1000mcg/L OR direct bilirubin \>0.4mg/dl but \<5xULN AND platelet count \<250,000/uL at baseline * Adequate organ functions as defined as: 1. ECOG performance status of 2 or better 2. Cardiac function: LVEF of 40% or greater 3. Pulmonary Function: Pulse oximetry with a baseline oxygen saturation of 85% or greater and corrected DLCO of 40% or greater 4. Hepatic Function: Serum conjugated (direct) bilirubin less than 5x upper limit of normal for age as per local laboratory, ALT and 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. 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 PBSC product for the HSCT of the recipient. 3. Donor cannot be pregnant or lactating and must agree to contraception until after the donation procedure is complete. 4. Testing negative for HIV and viral hepatitis 5. Free of Hb S (defined as Hb S less than 50%) and other hemoglobinopathies that are symptomatic or of clinical significance. 6. Targeted minimum stem cell dose of 5.0 x 10e6 CD34 cells/Kg of recipient weight 7. Fulfills standard criteria for eligibility as a donor for HSCT.	1. Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 40% of predicted OR baseline oxygen saturation of \<85% or PaO2 \<70. 2. Severe cardiac dysfunction defined as ejection fraction \<35%. 3. Impaired renal function defined as GFR \<40. 4. Hepatic dysfunction defined as bridging (portal to portal) fibrosis or cirrhosis of the liver OR transaminases \>5x ULN for age. 5. Clinical stroke within 6 months of anticipated transplant 6. Karnofsky performance score \< 50% 7. HIV infection 8. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment. 9. Have circulating HAMA noted on initial screening. 10. Have received prior radiation to maximally tolerated levels to any critical normal organs 11. Patients with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT. 12. Patients' unable to understand the nature and risks inherent in the HSCT process. 13. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation. 14. Patient is pregnant or lactating. 15. Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor. 16. Patients with any history of radiation therapy.

Inclusion Criteria

Exclusion Criteria

* Availability of an HLA-matched sibling donor
* Patients with sickle cell anemia (Hb SS, Sβ0 thalassemia or severe SC) who are 12 - 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 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 catherization.
6. Sickle hepatopathy defined as EITHER ferritin \>1000mcg/L OR direct bilirubin \>0.4mg/dl but \<5xULN AND platelet count \<250,000/uL at baseline
* Adequate organ functions as defined as:
1. ECOG performance status of 2 or better
2. Cardiac function: LVEF of 40% or greater
3. Pulmonary Function: Pulse oximetry with a baseline oxygen saturation of 85% or greater and corrected DLCO of 40% or greater
4. Hepatic Function: Serum conjugated (direct) bilirubin less than 5x upper limit of normal for age as per local laboratory, ALT and 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.
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 PBSC product for the HSCT of the recipient.
3. Donor cannot be pregnant or lactating and must agree to contraception until after the donation procedure is complete.
4. Testing negative for HIV and viral hepatitis
5. Free of Hb S (defined as Hb S less than 50%) and other hemoglobinopathies that are symptomatic or of clinical significance.
6. Targeted minimum stem cell dose of 5.0 x 10e6 CD34 cells/Kg of recipient weight
7. Fulfills standard criteria for eligibility as a donor for HSCT.

1. Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 40% of predicted OR baseline oxygen saturation of \<85% or PaO2 \<70.
2. Severe cardiac dysfunction defined as ejection fraction \<35%.
3. Impaired renal function defined as GFR \<40.
4. Hepatic dysfunction defined as bridging (portal to portal) fibrosis or cirrhosis of the liver OR transaminases \>5x ULN for age.
5. Clinical stroke within 6 months of anticipated transplant
6. Karnofsky performance score \< 50%
7. HIV infection
8. Uncontrolled viral, bacterial, fungal, or protozoal infection at the time of study enrollment.
9. Have circulating HAMA noted on initial screening.
10. Have received prior radiation to maximally tolerated levels to any critical normal organs
11. Patients with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT.
12. Patients' unable to understand the nature and risks inherent in the HSCT process.
13. History of non-compliance severe enough in the estimation of the treating team to preclude the patient from undergoing unrelated donor transplantation.
14. Patient is pregnant or lactating.
15. Inability to provide adequate transfusion support or increased risk immunohematological complications due presence of anti-RBC antibody against stem cell donor.
16. Patients with any history of radiation therapy.

Contacts and Locations

Study Contact

Central Nurse Navigator, RN

CONTACT

(212) 342 5162

cancerclinicaltrials@cumc.columbia.edu

Principal Investigator

Markus Y Mapara, MD

PRINCIPAL_INVESTIGATOR

Columbia University

Study Locations (Sites)

Columbia University Irving Medical Center

New York, New York, 10032

United States

Collaborators and Investigators

Sponsor: Columbia University

Markus Y Mapara, MD, 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 Date2025-04-28

Study Completion Date2032-03-12

Study Record Updates

Study Start Date2025-04-28

Study Completion Date2032-03-12

Terms related to this study

Keywords Provided by Researchers

severe sickle cell disease
severe SCD
sickle cell disease
sickle cell
advanced SCD
advanced sickle cell disease
anemia
sickle cell disorders
hemoglobin S (HbS) Disease
Hemoglobin S Disease

Additional Relevant MeSH Terms

Sickling Disorder Due to Hemoglobin S