Acute Myeloid Leukemia, Myelodysplastic Syndromes
Conditions
Brief summary
Phase 1/1b, open label, multi-center dose escalation and dose expansion study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 alone or in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53
Detailed description
Phase I, open label, multi-center dose escalation (DEP) and dose expansion (EXP) study designed to evaluate safety, tolerability, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumor effects of ALRN-6924 in patients with acute myeloid leukemia or advanced myelodysplastic syndrome with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt interaction between the p53 tumor suppression protein and its endogenous inhibitors murine double minute 2 (MDM2) and murine double minute X (MDMX) Men and women 18 years of age and older with relapsed or refractory acute myeloid leukemia or advanced myelodysplastic syndrome and for which standard treatment(s) are not available or are no longer effective can be enrolled. Treatment of patients in the DEP and EXP phases will continue in the study until documentation of disease progression, unacceptable toxicity, or patient or physician decision to discontinue study participation is made.
Interventions
DRUGALRN-6924
Fixed dose of ALRN-6924 per cohort, administered IV, Days 1, 8, and 15 every 28 days.
DRUGALRN-6924 in combination with cytarabine
Cytarabine (100 or 200 mg/m2) will be administered as an IV infusion followed by ALRN-6924 on Days 1, 8, and 15 every 28 days.
Sponsors
Aileron Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Relapsed or refractory acute myeloid leukemia or IPSS-R intermediate/high/very high-risk MDS patients * Confirmed or anticipated wild-type TP53 * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Adequate hepatic and renal function * Acceptable coagulation function * Negative serum or urine pregnancy test within 7 days prior to the first dose of ALRN-6924 for women of child-bearing potential * Sufficient wash out from prior therapies and recovery from all significant toxicities
Exclusion criteria
* Patients are eligible for available approved standard therapies * Prior treatment with MDM2 inhibitor, with protocol specified exceptions * Patients with history of allogeneic stem cell transplantation * Leukemic blast counts of \>25,000/µl * Deletion of chromosome 17, or del(17p) * Patients with evidence of current central nervous system leukemic involvement * Known hypersensitivity to any study drug component * History of coagulopathy * Prior specified cardiovascular risk factors * Clinically significant gastrointestinal bleeding within 6 months * Clinically significant third-space fluid accumulation * Pregnant or lactating females * Evidence of any serious and/or unstable pre-existing medical condition that would interfere with patient safety ability to provide informed consent * Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C * Second malignancy within one year, with protocol specified exceptions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the safety and tolerability of ALRN-6924 alone and in combination with cytarabine | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days) | Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0 |
| Determine maximum tolerated dose (MTD) | From the first dose until the end of Cycle 2 (each cycle is 28 days) | Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with AML or MDS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine immunogenicity of ALRN-6924 | Approximately 16 weeks | Incidence of anti-ALRN-6924 antibodies |
| Determine PK parameters of ALRN-6924 when administered to patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS) | First 2 cycles (each cycle is 28 days) | Peak Plasma Concentration (Cmax) |
| Determine best overall response, duration of response, morphologic leukemia-free state, leukemia free survival, percentage of MDA patients who have achieved hematologic improvement, changes in transfusion rate and early death rate | Approximately 16 weeks | International Working Group (IWG) Criteria (Cheson et al, 2006) |
Countries
United States
Outcome results
None listed