Status:
TERMINATED
Study to Investigate the Pharmacokinetics, Pharmacodynamics and Assess the Efficacy and Safety to Support Dose Selection of Emapalumab in Pre-empting Graft Failure in Patients at High Risk After HSCT.
Lead Sponsor:
Swedish Orphan Biovitrum
Collaborating Sponsors:
PRA Health Sciences
Cytel Inc.
Conditions:
Graft Failure
Eligibility:
All Genders
1+ years
Phase:
PHASE2
Brief Summary
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presen...
Detailed Description
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presen...
Eligibility Criteria
Inclusion
- Informed consent form signed by the patient (as required by law) or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable
- Recipients of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) and at high risk of graft failure (GF) based on at least one of the following criteria:
- Receiving reduced intensity conditioning (RIC) or non-myeloablative conditioning (NMA) combined with a non-malignant disease or with a graft from Bone Marrow (BM)
- Ex vivo T cell depleted graft
- Graft from mismatched unrelated or haploidentical donor
- Graft from Umbilical Cord Blood (UCB)
- Patients requiring allo-HSCT with the following underlying diseases:
- Malignant disease with high risk of GF, i.e. Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) with primary induction failure, second partial remission or relapse; Chronic Myeloid Leukemia (CML) in blastic phase (circulating blast or blast above 5% in biopsy); Non Hodgkin and Hodgkin Lymphoma and multiple myeloma with primary induction failure, second partial remission or relapse, myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) with splenomegaly, myelofibrosis with portal hypertension pre-transplant, MDS/MPD overlap syndromes
- Non-malignant hematological diseases (e.g. autoimmune and metabolic disorders, aplastic anemia, Sickle cell anemia, Fanconi anemia, Diamond-Blackfan anemia, thalassemia, osteopetrosis, Wiskott-Aldrich syndrome, severe combined immunodeficiency, Hemophagocytic lymphohistiocytosis and other immunoregulatory disorders)
- Male and female patients
- Children aged at least 1 year and adults. Once the appropriate dose has been determined in one of the three cohorts and safety has been assessed by the Independent Data Monitoring Committee (IDMC), children less than 1 year old may be included in the study.
- Females of child-bearing potential, defined as all women physiologically capable of becoming pregnant, require use of highly effective contraceptive measures from screening until 6 months after the last study drug administration
Exclusion
- Pregnant (or planning to become pregnant) or lactating female patients
- Body weight \< 3 kg
- Underlying malignant disease with Karnofsky/Lansky performance status equal or less than 40 or an Eastern Cooperative Oncology Group (ECOG) performance status equal or less than 3
- Patients presenting CXCL9 levels 10 times above the upper limit of the 95% interval (CI) of the normal range (reported in the CXCL9 assay laboratory manual) within 24 hours prior to HSCT
- Clinically manifested infections caused by typical and atypical Mycobacteria, Salmonella, Histoplasma capsulatum and Herpes Zoster on the day of HSCT
- Active or clinical suspicion of latent tuberculosis
- Concomitant diseases that in the opinion of the Investigator may interfere with the assessment of emapalumab safety or efficacy
- Receipt of a Bacille Calmette-Guerin (BCG) vaccine within 3 months prior to HSCT
- Receipt of a live or attenuated live (other than BCG) vaccine within 6 weeks prior to HSCT
- Current or scheduled administration of therapies known to potentially trigger a cytokine release syndrome within 21 days from HSCT.
- Patients having received IFNγ during the last 2 weeks prior to HSCT and/or who require treatment with IFNγ.
- Patients having received emapalumab during the last 6 months prior to HSCT, unless it is known that emapalumab is no longer detectable.
- Patients having received kinase inhibitors (Janus kinase inhibitors \[JAKi\] or bruton tyrosine kinase inhibitors \[BTKi\]) one week (or 5 half-lives whichever is greater) prior to HSCT.
- Intolerance to antimicrobial and virus infection prophylaxis.
- Hypersensitivity to emapalumab or any of the excipients.
- Ongoing participation in an interventional trial or administration of any investigational drug (within 3 half-lives of the investigational drug) with the exception of interventional trials involving supportive care such as probiotics or antiemetics, graft manipulation, or use of new combinations or new dosing of conventional therapies for conditioning and prophylaxis pre-HSCT.
Key Trial Info
Start Date :
May 25 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 21 2022
Estimated Enrollment :
2 Patients enrolled
Trial Details
Trial ID
NCT04731298
Start Date
May 25 2021
End Date
April 21 2022
Last Update
December 28 2023
Active Locations (5)
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1
Peter MacCallum Cancer Centre
Melbourne, Australia, 3000
2
Kids Cancer Centre Sydney Children's Hospital
Randwick, Australia, 2031
3
CHU Sainte-Justine
Montreal, Quebec, Canada, H3T 1C5
4
The Rambam Academic Hospital
Haifa, Israel, 31096