Emapalumab for the Treatment of Pediatric Patients with Aplastic Anemia
This phase IIa/b trial tests how well emapalumab given upfront works in treating pediatric patients with severe acquired aplastic anemia (sAA). sAA is a condition of the immune system that results in hematopoietic stem cells (HSCs) being destroyed and the body being unable to produce blood cells. The standard treatment options for sAA are immune suppression therapy (IST) or hematopoietic stem cell transplant (HCT), but neither treatment can be started right away after diagnosis. addition, the inflammation caused by sAA can affect how well these treatments work. Emapalumab is an antibody, like the proteins made by the immune system to protect the body from harm. Emapalumab blocks the protein interferon gamma (INF-gamma), which activates the immune system and increases inflammation. By blocking INF-gamma, emapalumab may decrease inflammation, reduce symptoms, and help standard IST and HCT work better. Giving emapalumab as upfront treatment (after diagnosis and before standard IST or HCT) may be effective in treating pediatric patients with sAA.
Inclusion Criteria
- Patients undergoing workup for suspected newly diagnosed sAA: * Patients with severe cytopenias and a hypocellular marrow concerning for sAA * Patients that meet the definition for suspected sAA (Camitta criteria) as follows: ** Marrow cellularity: < 25%, or 25-50% with < 30% residual hematopoietic cells ** Peripheral cytopenias (at least 2 of 3) *** Absolute neutrophil count (ANC): < 500 x 10^9/L *** Platelets: < 20 x 10^9/L *** Absolute reticulocyte count: < 60 x 10^9/L
- Patients that do not have evidence of leukemia or myelodysplastic syndrome (MDS)
- Patients ≤ 25 years of age at time of diagnosis
- Able to tolerate emapalumab and IST (with standard institutional organ function criteria)
Exclusion Criteria
- Uncontrolled infection at presentation
- Patients who have undergone previous treatment for sAA
- Patients with known inherited bone marrow failure
- Patient who has completed a full workup for sAA including having results back from telomere testing, diepoxybutane (DEB) and genetics (when applicable), as well as having an appropriate willing and available donor and would otherwise be admitted for HSCT within 2 weeks of enrolling on the trial
- Patients with leukemia or MDS
- Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests
Additional locations may be listed on ClinicalTrials.gov for NCT06430788.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
Uniondale
West Harrison
Ohio
Cincinnati
Pennsylvania
Philadelphia
Virginia
Richmond
Wisconsin
Milwaukee
PRIMARY OBJECTIVES:
I. To assess the effects of an early upfront targeted intervention with emapalumab on hematologic parameters in patients with newly diagnosed sAA. (Phase 2a)
II. To assess if emapalumab treatment can increase response to IST to 80% partial and complete responders. (Phase 2b)
SECONDARY OBJECTIVES:
I. Determine overall survival (OS), event free survival (EFS), and relapse at 1 & 2 years. (Phase 2a, Emapalumab Window)
II. Determine incidence and dynamics of clonal hematopoiesis growth from initial diagnostic evaluation to end of upfront emapalumab window. (Phase 2a, Emapalumab Window)
III. Determine what percentage of patients are eligible to proceed to IST after early upfront emapalumab treatment. (Phase 2a, Emapalumab Window)
IV. Determine time to neutrophil, platelet and hemoglobin improvement through end of 6-week emapalumab window. (Phase 2a, Emapalumab Window)
V. Determine pharmacokinetic (PK) model for emapalumab in sAA. (Phase 2a, Emapalumab Window)
VI. Evaluate effect of emapalumab on bone marrow cellularity. (Phase 2a, Emapalumab Window)
VII. Determine effect of emapalumab on lymphocyte subsets, inflammatory markers, CXCL9 and pro-inflammatory cytokines. (Phase 2a, Emapalumab Window)
VIII. To describe patient reported outcome (PRO) (global health, mental health, physical health, social health measures) using Patient-Reported Outcomes Measurement Information System (PROMIS) as an opt-in study in patients ≥ 5 years of age. (Phase 2a, Emapalumab Window)
IX. Determine overall survival (OS), event free survival (EFS), and relapse at 1 & 2 years. (Phase 2b, IST)
X. Hematologic response to IST at 12 and 52 weeks post-equine anti-thymocyte globulin (hATG) infusion. (Phase 2b, IST)
XI. Determine incidence of all clonal hematopoiesis and pre-malignant clonal hematopoiesis at 1-year post-IST. (Phase 2b, IST)
XII. Determine time to neutrophil, platelet and hemoglobin recovery at 6 months post-IST. (Phase 2b, IST)
XIII. Determine plasma levels of CXCL9 and pro-inflammatory cytokines through 6 months post-IST. (Phase 2b, IST)
XIV. Determine lymphocyte subsets through 6 months post-IST. (Phase 2b, IST)
XV. To describe the patient reported outcome (PRO) (global health, mental health, physical health, social health measures) using Patient-Reported Outcomes Measurement Information System (PROMIS) as an opt-in study in patients ≥ 5 years of age. (Phase 2b, IST)
XVI. Determine the safety profile of emapalumab given in conjunction with hATG and cyclosporine. (Phase 2b, IST)
XVII. Estimate the response rate in patients receiving emapalumab followed by HCT. (Phase 2b, bone marrow transplant [BMT])
XVIII. Estimate the response rate in patients receiving emapalumab followed by HCT. (Phase 2b, BMT)
XIX. Determine overall survival (OS), event free survival (EFS), and relapse at 1 & 2 years. (Phase 2b, BMT)
XX. Estimate incidence of acute graft versus host disease (GVHD) (according to Memorial Sloan Kettering [MSK] guidelines) at day +100, +180, and 1-year follow-up. (Phase 2b, BMT)
XXI. Estimate incidence of chronic GVHD (according to MSK guidelines) at +180, and 1-year follow-up. (Phase 2b, BMT)
XXII. Determine the time to neutrophil engraftment defined as the first of 3 consecutive days of absolute neutrophil count (ANC) ≥ 500 K/uL. (Phase 2b, BMT)
XXIII. Determine the time to platelet engraftment defined as the first of 7 consecutive days with a platelet count exceeding 20,000/uL without transfusion support. (Phase 2b, BMT)
XXIV. Determine incidence of primary engraftment failure (failure to achieve neutrophil engraftment by day 30 after transplantation). (Phase 2b, BMT)
XXV. Determine incidence of secondary engraftment failure (defined as < 500/uL circulating neutrophils at any time after primary engraftment that is not attributed to disease recurrence or drug therapy). (Phase 2b, BMT)
XXVI. Determine kinetics of donor chimerism. (Phase 2b, BMT)
XXVII. Evaluate the incidence of grade ≥ 3 non-hematologic adverse events by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 by day +100, +180, and 1 year post allogeneic (allo)-HCT. (Phase 2b, BMT)
XXVIII. To determine lymphocyte subset reconstitution by evaluation of lymphocyte subsets (immune function). (Phase 2b, BMT)
XXIX. To describe the patient reported outcome (PRO) (global health, mental health, physical health, social health measures) using Patient-Reported Outcomes Measurement Information System (PROMIS) as an opt-in study in patients ≥ 5 years of age. (Phase 2b, BMT)
OUTLINE:
Patients receive emapalumab intravenously (IV) over 1-2 hours once a week (QW) for up to 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with hematologic response receive standard of care (SOC) IST with equine anti-thymocyte globulin (hATG) and cyclosporin (CsA) and then receive emapalumab IV QW for up to 6 doses in the absence of disease progression or unacceptable toxicity. Patients with no hematologic response receive HCT per institutional SOC. Patients that are found to have a matched sibling donor (MSD) while receiving emapalumab may complete the 6 weeks of emapalumab treatment or may be stopped early (at discretion of treating physician) and receive MSD HCT. Patients also undergo bone marrow aspiration and/or bone marrow biopsy, bone marrow, and blood sample collection throughout the study.
After completion of study treatment, patients are followed up to 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorAndromachi Scaradavou
- Primary ID23-278
- Secondary IDsNCI-2024-04692
- ClinicalTrials.gov IDNCT06430788