Acute Myeloid Leukemia MedDRA version: 21.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent must be obtained prior to participation in the study. 2. Adults >/= 18 years of age. 3. Participants with AML diagnosis, who underwent one allo-SCT to treat AML and are currently at Day >/=60 but no later than Day 120 (/=60 and /=CR2) prior to allo-SCT. • AML in complete morphologic • remission (/= 45 mL/min/1.73 m2) (within 14 days prior to start of study treatment). 11. Evidence of adequate engraftment post allo-SCT: ANC >/= 1.0x109/L, platelet count >/= 75x109/L, hemoglobin = 8 g/dL (within 14 days prior to start of study treatment). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Prior exposure to MDM-inhibitor. 2. Active acute GvHD of any grade (per Harris et al 2016) requiring systemic therapy at time of study treatment initiation. 3. Active chronic GvHD of any grade (per NIH criteria (Jagasia et al 2015)) requiring systemic therapy at time of study treatment initiation. 4. Past history of grade III or IV acute GvHD (per Harris et al 2016) and/or past history of moderate or severe chronic GvHD (per NIH criteria (Jagasia et al 2015)). 5. Recipient of allo-SCT from a matched unrelated donor (MUD) with one or more antigen or allele mismatch at HLA-A, -B, -C, -DRB1 locus (HLA matching less than 8/8 antigens). 6. Recipient of allo-SCT from a haploidentical family donor. 7. Recipients of cord blood transplant as a graft source. 8. Prior systemic cancer-directed treatments or investigational modalities 470 ms. • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA Grade III/IV). 15. Other concurrent severe and/or uncontrolled medical conditions or serious organ dysfunction or other co-morbidity that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety Primary Objectives: • To determine the dose and schedule of siremadlin monotherapy that is tolerable without unacceptable toxicities (recommended dose for priming), measured by incidence of dose-limiting toxicities (DLTs). • To determine the dose and schedule of siremadlin in combination with DLI that is tolerable without unacceptable toxicities (maximum recommended dose for combination), measured by time to DLT. Efficacy Primary Objectives: • To evaluate the preliminary efficacy of siremadlin (priming monotherapy, in combination with DLI after priming monotherapy and as monotherapy maintenance subsequent to priming or combination with DLI) on prevention of hematologic relapse, measured by the proportion of participants who are alive and maintained CR or CRi with no evidence of hematologic relapse over at least 6 months after start of study treatment.;Secondary Objective: • To assess relapse free survival (RFS). • To assess cumulative incidence of relapse at 1 year and at 2 years after start of study treatment. • To assess overall survival (OS). • To assess the effect of study treatment on MRD status within the first 6 months of study treatment. • To assess safety and tolerability of siremadlin monotherapy (during priming and maintenance) and in combination with DLI. • To assess the proportion of participants stopping study treatment due to GvHD or other adverse events. • To assess the incidence of grade III and IV acute graft vs host disease (GvHD), moderate and severe chronic GvHD. • To assess GvHD-free/relapse-free survival (GRFS). • To characterize the pharmacokinetics of siremadlin in monotherapy and in combination with DLI.;Primary end point(s): Safety: • Incidence of DLTs with siremadlin monotherapy in priming phase • Time to DLT with siremadlin/DLI in combination phase Efficacy: • Proportion of participants who are alive and maintained CR or CRi with no evidence of hematologic relapse over at least 6 months after start of study tre | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Time from start of study treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first • Cumulative incidence of AML relapse at 1 year and at 2 years after start of study treatment • Time from start of study treatment to the date of death from any cause. • MRD status of participants at baseline and within the first 6 months of study treatment • Incidence and severity of AEs and SAEs, changes in laboratory values and vital signs. • Proportion of participants with permanent discontinuation of study treatment due to GvHD or other adverse events. • Incidence of treatment emergent grade III or grade IV aGvHD. Incidence of treatment emergent moderate to severe cGvHD. • Time from start of study treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD, cGvHD requiring initiation of systemic immunosuppressive treatment, occurence of disease relapse, or death due to any cause, whichever occurs first. • Pharmacokinetic parameters (e.g., AUC, Cmax, Tmax) and concentration vs time profiles of siremadlin in monotherapy and in combination with DLI.;Timepoint(s) of evaluation of this end point: The secondary endpoints will be evaluated at the primary efficacy analysis and final analysis (at the end of study): Time point for PK in monotherapy is both primary efficacy analysis and final analysis (end of study), while time point for PK in combination with DLI is final analysis. | — |
Countries
Australia, Germany, Israel, Italy, Spain, United Kingdom, United States
Contacts
Public ContactTrial Monitoring Organization (TMO)
Novartis Farmacéutica, S.A.
Outcome results
None listed