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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05447663




Registration number
NCT05447663
Ethics application status
Date submitted
28/06/2022
Date registered
7/07/2022
Date last updated
3/05/2024

Titles & IDs
Public title
A Study of Siremadlin Alone and in Combination With Donor Lymphocyte Infusion in Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplant
Scientific title
A Phase Ib/II, Open Label Study of Siremadlin Monotherapy and in Combination With Donor Lymphocyte Infusion as a Treatment for Patients With Acute Myeloid Leukemia Post-allogeneic Stem Cell Transplantation Who Are in Complete Remission But at High Risk for Relapse.
Secondary ID [1] 0 0
2021-003596-34
Secondary ID [2] 0 0
CHDM201K12201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stomach Adenocarcinoma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Comparator / control treatment
Control group

Outcomes

Eligibility
Key inclusion criteria
* Participants with AML diagnosis, who underwent one allo-SCT to treat AML and are currently at = Day 60 but no later than Day 120 (= Day 120) post allo-SCT.
* Pre-allo-SCT - Participants must have any of the following risk factors that put them at high risk for relapse:

• AML in first CR (CR1) prior to allo-SCT with one of the following:
* Adverse risk genetic abnormalities per 2017 ELN risk stratification. Patients with TP53 mutant AML at diagnosis are eligible if they meet eligibility criteria.
* Therapy-related AML (t-AML).
* Secondary AML (sAML) [AML secondary to antecedent myelodysplastic syndrome (MDS) or AML secondary to myeloproliferative neoplasm (MPN)].

• AML in second or greater CR (=CR2) prior to allo-SCT.
* Allo-SCT must have the following characteristics:

* Unmanipulated/T cell-replete bone marrow or peripheral blood stem cells as a graft source.
* Matched related (family) donor (MFD) or matched unrelated donor (MUD): Human Leukocyte Antigen (HLA) matching of donor and recipient should be at a minimum of 8/8 antigen or allele matched at HLA-A, -B, -C, -DRB1 loci.
* Any conditioning regimen intensity is permitted, the use of anti-thymocyte globulin (ATG) or alemtuzumab or post-transplant cyclophosphamide as a part of conditioning is allowed.
* Donor lymphocytes are collected, cryopreserved and available for infusion (DLI), or obtaining donor lymphocytes for DLI is feasible (applicable only for part 2)
* Post-allo-SCT, participants must have achieved CR or CRi with no current evidence of hematologic relapse
* Eastern Cooperative Oncology Group (ECOG ) performance status 0, 1 or 2.
* Laboratory test results indicating adequate liver and kidney function laboratory test results
* Evidence of adequate engraftment: Absolute Neutrophil Count (ANC) = 1.0x109/L, Platelets (PLT) = 75x109/L, Hemoglobin (Hgb) = 8 g/dL (within 14 days prior to start of study treatment)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Prior exposure to MDM-inhibitor
* Active acute GvHD (aGvHD) of any grade (per Harris et al 2016) and/or active chronic GvHD (cGvHD ) of any grade (per NIH criteria (Jagasia et al 2015)) requiring systemic therapy at time of study treatment initiation
* Past history of grade III or IV aGvHD and/or past history of moderate or severe cGvHD. History of lower grades of GvHD is permitted if GvHD resolved to grade 0 for at least 4 weeks prior to start of study treatment.
* Recipient of allo-SCT from MUD with =1 antigen or allele mismatch at HLA-A, -B, -C, -DRB1 locus (HLA matching < 8/8 antigens)
* Recipient of allo-SCT from a haploidentical family donor; and recipients of cord blood transplant as a graft source
* Prior systemic AML-directed treatments given at any time after allo-SCT (including DLI)
* Prior systemic cancer-directed treatments or investigational modalities = 5 half-lives or 4 weeks prior to starting study, whichever is longer
* GI disorders that may prevent the intake and absorption of oral siremadlin (eg, diarrhea, uncontrolled nausea/vomiting, GI bleeding, etc).
* Any concurrent severe and/or active uncontrolled bacterial, viral or fungal infection requiring parenteral antibacterial, antiviral or antifungal therapy. Prophylactic antimicrobial use (oral or parenteral) is allowed.
* Participants who require treatment with moderate or strong CYP3A inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A inducers during the entire study
* Cardiac or cardiac repolarization abnormality, that are clinically significant

Other protocol defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/02/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
26/10/2023
Sample size
Target
Accrual to date
Final
8
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study was to confirm a safe dose and schedule as well as the preliminary efficacy of siremadlin alone, and in combination with donor lymphocyte infusion (DLI), in adult participants with AML who are in remission following allogeneic stem cell transplantation (allo-SCT) but are at high risk for relapse based on the presence of pre-transplant risk factors.
Trial website
https://clinicaltrials.gov/study/NCT05447663
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05447663