HDM201 Added to CT in R/R or Newly Diagnosed AML
Status and phase
Withdrawn
Phase 2
Phase 1
Conditions
Leukemia, Myeloid, Acute
Treatments
Drug: HDM201
Drug: cytarabine
Drug: posaconazole
Drug: liposomal cytarabine/daunorubicin
Drug: midazolam
Drug: midostaurin
Drug: anthracycline
Study type
Interventional
Funder types
Industry
Identifiers
Details and patient eligibility
About
This is a multi-center open-label Phase I/II study investigating orally administered HDM201 in combination with chemotherapy in two populations: subjects with first line AML or subjects with relapsed/refractory AML. This study is conducted in three parts: dose escalation, dose expansion and DDI study.
Full description
This is a Phase 1 / 2 study. No patients were screened / enrolled. There are no data collected. There will be no CSR.
Sex
All
Ages
18+ years old
Volunteers
No Healthy Volunteers
Inclusion criteria
All Subjects
- Signed informed consent must be obtained prior to participation in the study
- Age ≥18
- Diagnosis of AML based on WHO 2016 classification. Patients with APL (acute promyelocytic leukemia) with PML-RARA are not eligible.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) that is 0 - 2.
- Adequate organ functions
- Left ventricular ejection fraction > 45%
For 1L AML population:
- For Part 1 or Part 2 Expansion Cohorts 1 or 2: subjects with de novo AML suitable for induction treatment with cytarabine and anthracyclines as per investigator judgement
- For Part 2 Expansion Cohort 2: documented presence of FLT3 mutation (ITD or TKD ) and suitable for midostaurin treatment as per investigator judgement.
- For Part 2 Expansion Cohort 3: Subjects with secondary AML (e.g. AML-MRC , secondary to myelodysplasia/MDS or therapy-related AML). Prior use of hypomethylating agents or other therapies with curative intent for treatment previous hematological malignancies or therapy-related AML is allowed. Subjects suitable for induction treatment with liposomal cytarabine/daunorubicin as per investigator judgement.
For R/R AML population:
- All Parts: Diagnosis of relapsed or refractory AML and suitable for treatment with IDAC as per investigator judgement.
- For Part 3 only: willingness and suitability to participate in DDI Cohort 1 or 2.
Exclusion criteria
- Prior exposure to MDM2 and MDM4 inhibitor (e.g. idasanutlin)
- Known symptomatic CNS leukemia not controlled by adequate therapy.
- Isolated extramedullary leukemia
- Subjects with prior malignancy (some exceptions apply)
- QTcF > 470 ms at screening
- Subjects who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment or during the study
- Subjects who require use of herbal preparations/medications and dietary supplements within 7 days prior to first dose and during the study
- Subjects who require treatment with substrates of CYP3A4/5 with narrow therapeutic index (within 24 hours prior to during and 48 hours after HDM201 administration)
- Subjects who require treatment with moderate or strong CYP3A4 inhibitors within 48 hours prior to, during and 48 hours post HDM201 administration. (except for Part 3 DDI Cohort 1 and 2)
- Subject is pregnant or breastfeeding
- WOCBP unless using highly effective methods of contraception during study treatment and for an appropriate time period after last study treatment
- Sexually active males unless they use a condom during intercourse while taking study drug and for an appropriate time period after last study treatment
For Part 1 only:
- Subjects with a known favorable risk AML subtype at screening or subjects with FLT3 mutation
For Part 3 only:
- DDI Cohort 1: use of posaconazole (other than the planned dosing required by the protocol) within 7 days prior to start of the DDI investigation and for the duration of the DDI period
- DDI Cohort 2: use of midazolam (other than the planned dosing required by the protocol) within 2 days prior to start of the DDI investigation and for the duration of the DDI period
- DDI Cohort 1 and 2: subjects who have received, or are expected to receive moderate or strong inhibitors of CYP3A4 within 7 days prior to start of the DDI investigation, for the duration of the investigation, and 24 hours after last blood sample collection for PK assessment
Other protocol-defined inclusion/exclusion may apply.
Trial design
Primary purpose
Treatment
Allocation
Non-Randomized
Interventional model
Parallel Assignment
Masking
None (Open label)
0 participants in 8 patient groups
Part 1 - first line (1L) AML
Experimental group
Description:
1L acute myeloid leukemia (AML) subjects receiving HDM201 in various doses/schedules in combination with cytarabine/anthracyclines
Treatment:
Drug: anthracycline
Drug: cytarabine
Drug: HDM201
Part 1 - relapsed/refractory (R/R) AML
Experimental group
Description:
R/R AML subjects receiving HDM201 in various doses/schedules in combination with cytarabine
Treatment:
Drug: cytarabine
Drug: HDM201
Part 2 - Expansion Cohort 1
Experimental group
Description:
1L de novo AML subjects without documented FLT3 mutation receiving HDM201 at the recommended dose of expansion (RDE) in combination with cytarabine/anthracyclines
Treatment:
Drug: anthracycline
Drug: cytarabine
Drug: HDM201
Part 2 - Expansion Cohort 2
Experimental group
Description:
1L de novo AML subjects with documented FLT3 mutation status receiving HDM201 at RDE in combination with cytarabine/anthracyclines and midostaurin
Treatment:
Drug: anthracycline
Drug: midostaurin
Drug: cytarabine
Drug: HDM201
Part 2 - Expansion Cohort 3
Experimental group
Description:
1L secondary AML subjects receiving HDM201 at RDE in combination with liposomal cytarabine/daunorubicin
Treatment:
Drug: liposomal cytarabine/daunorubicin
Drug: cytarabine
Drug: HDM201
Part 2 - Expansion Cohort 4
Experimental group
Description:
R/R AML subjects receiving HDM201 at RDE in combination with cytarabine
Treatment:
Drug: cytarabine
Drug: HDM201
Part 3 - DDI Cohort 1
Experimental group
Description:
R/R AML subjects receiving HDM201 at adjusted recommended Phase 3 dose (RP3D) determined in Part 2 in combination with cytarabine and posaconazole added in Cycle 1
Treatment:
Drug: posaconazole
Drug: cytarabine
Drug: HDM201
Part 3 - DDI Cohort 2
Experimental group
Description:
R/R AML subjects receiving HDM201 at RP3D in combination with cytarabine and midazolam
Treatment:
Drug: midazolam
Drug: cytarabine
Drug: HDM201
Trial contacts and locations
0
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Data sourced from clinicaltrials.gov
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