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

ConditionSickling Disorder Due to Hemoglobin S
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age12-50
SponsorColumbia University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Availability of an HLA-matched sibling donor

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).

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • 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.

  • 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.

  • 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.

  • Total Body Irradiation

    Radiation

    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.

  • Exchange Transfusion

    Procedure/Surgery

    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).

  • 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.

Treatment groups

24 Participants
are divided into 1 treatment group
Group A: 131I-apamistmab-based nonmyeloablative conditioningExperimental treatment 6 interventions

Trial outcomes

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%.

Time frame
42 days after blood stem cell (PB) transplantation

Secondary outcomes

1

Event-free survival (EFS) Rate

Event-free survival is defined as the time from treatment initiation to the occurrence of primary graft failure, death, Graft-versus-Host Disease (GVHD) Grade III-IV, whichever comes first. Patients without events will be censored at the time of last follow-up assessment.

Time frame
Duration of study, up to 7 years
2

Time to engraftment of Neutrophils

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 frame
Up to 7 years
3

Time to engraftment of Platelets

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. The exception is the case in which a subject is given a platelet transfusion specifically to achieve a platelet threshold to allow an elective invasive procedure, such as a central catheter removal. Time from treatment initiation to successful donor cell engraftment defined as having achieved \> 50% total Peripheral Blood Mononuclear Cells (PMC) donor cell chimerism upon successful engraftment at day +30 or upon meeting ANC and Plt engraftment whatever occurs first.

Time frame
Up to 7 years
4

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

Incidence of acute and chronic GVHD of any grade as evaluated according to The Center for International Blood and Marrow Transplant Research (CIBMTR) and National Institutes of Health (NIH) criteria respectively.

Time frame
Up to 7 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Columbia University

Lead sponsor

Actinium Pharmaceuticals

Collaborator

Source ClinicalTrials.gov
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