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

NCT07015684 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: AAAV1172
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Sickling Disorder Due to Hemoglobin S

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Graft failure rate

  Graft failure defined as having had a primary or secondary graft failure by 42 days after blood stem cell (PB) transplantation. Primary graft failure is defined as failure to achieve an absolute neutrophil count (ANC) of \>500/ μL by 42 days after blood stem cell (PB) transplantation or a total donor chimerism of \>5%. Secondary graft failure is defined as cytopenias after initial engraftment (ANC \<500/μL) and a total donor cell chimerism decreasing to less than 5%.

  42 days after blood stem cell (PB) transplantation

Secondary Outcomes (13)

• Event-free survival (EFS) Rate

  Duration of study, up to 7 years

• Time to engraftment of Neutrophils

  Up to 7 years

• Time to engraftment of Platelets

  Up to 7 years

• Incidence of Graft-versus-Host Disease (GVHD) of any grade

  Up to 7 years

• Incidence of other transplant related toxicities

  12 Months Post Stem Cell Transplant

Study Arms (1)

131I-apamistmab-based nonmyeloablative conditioning

EXPERIMENTAL

Ten days before participants receive donor stem cell infusion, they will receive a dose of 131 I-apamistamab as an intravenous (IV) infusion into a vein in the arm. The 131 I-apamistamab product will be formulated in advance of the anticipated infusion date, for infusion on a specific date, based on target dose (100 mCi or 150 mCi, based on dose level).

Drug: 131I-apamistmab; Drug: Sirolimus; Drug: Campath; Drug: Total Body Irradiation; Procedure: Exchange Transfusion; Radiation: Planar gamma imaging

Interventions

131I-apamistmab DRUG

131I-apamistamab is a drug construct consisting of the apamistamab monoclonal antibody (mAb) and radioactive isotope iodine 131 (131I). The study drug will be patient-specific and will be manufactured for dosing on a specific date. The antibody dose will be at least 0.5mg/kg, however the final antibody amount may be higher if necessary based on the target radioactivity level. The 131I-apamistamab study drug requires patient details such as height, weight, a calculation to determine weight for use in calculating antibody amount for the dose. 131I-apamistmab will be given via intravenous (IV) infusion.

Also known as: Iodine (131I) apamistamab

131I-apamistmab-based nonmyeloablative conditioning

Sirolimus DRUG

Sirolimus is a macrocyclic lactone produced by Streptomyces hygroscopicus. It is an immunosuppressant agent. Sirolimus is to be given orally either as tablet or solution form. Dosage will be adjusted to a therapeutic target of 10-15 ng/mL in first 6 months post-transplant and 5-10 ng/mL after 6 months.

Also known as: Rapamycin, Rapamune

131I-apamistmab-based nonmyeloablative conditioning

Campath DRUG

Campath is a recombinant DNA-derived humanized monoclonal antibody that is directed against the 21-28 kD cell surface glycoprotein, CD52. CD52 is expressed on the surface of normal and malignant B and T lymphocytes, NK cells, monocytes, macrophages, and tissues of the male reproductive system. Campath will be given via IV at a total dose of 1 mg per kilogram of body weight.

Also known as: Alemtuzumab

131I-apamistmab-based nonmyeloablative conditioning

Total Body Irradiation DRUG

Radiation dose is 3Gy (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

131I-apamistmab-based nonmyeloablative conditioning

Exchange Transfusion PROCEDURE

Patient will undergo a red blood cell (RBC) exchange transfusion to achieve a Hemoglobin S (HgbS) level \< 20% prior to starting therapy to prevent the development of a vaso-occlusive Crisis (VOC).

131I-apamistmab-based nonmyeloablative conditioning

Planar gamma imaging RADIATION

Dosimetric imaging will be performed using quantitative planar gamma camera acquisition. Planar gamma imaging is a technique used in medical imaging to take pictures of the inside of the body, particularly to look at how certain organs or tissues are functioning. This allows the study doctor to evaluate how the study drugs are absorbed into the body.

Also known as: therapeutic radiation

131I-apamistmab-based nonmyeloablative conditioning

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• 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 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 catherization.
• 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:
• ECOG performance status of 2 or better
• Cardiac function: LVEF of 40% or greater
• Pulmonary Function: Pulse oximetry with a baseline oxygen saturation of 85% or greater and corrected DLCO of 40% or greater
• 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.
• 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.
• Donor Eligibility and Selection Criteria

You may not qualify if:

• Pulmonary dysfunction defined as DLCO (corrected for hemoglobin and alveolar volume) \< 40% of predicted OR baseline oxygen saturation of \<85% or PaO2 \<70.
• Severe cardiac dysfunction defined as ejection fraction \<35%.
• Impaired renal function defined as GFR \<40.
• Hepatic dysfunction defined as bridging (portal to portal) fibrosis or cirrhosis of the liver OR transaminases \>5x ULN for age.
• 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.
• Have circulating HAMA noted on initial screening.
• Have received prior radiation to maximally tolerated levels to any critical normal organs
• Patients with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate HSCT.
• Patients' 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.

Sponsors & Collaborators

• Columbia University: lead
• Actinium Pharmaceuticals: collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell; Anemia; Sickle Cell Trait; Disease

Interventions

Iodine; Sirolimus; Alemtuzumab; Whole-Body Irradiation; Exchange Transfusion, Whole Blood

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; 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)

Halogens; Elements; Inorganic Chemicals; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques; Blood Transfusion; Biological Therapy

Study Officials

• Markus Y Mapara, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Central Nurse Navigator, RN

CONTACT

(212) 342 5162; cancerclinicaltrials@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Director of Bone Marrow Transplantation & Cell Therapy Program

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: June 11, 2025
• Study Start: April 28, 2025
• Primary Completion (Estimated): March 12, 2030
• Study Completion (Estimated): March 12, 2032
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

US (1)