A Single-arm, Multi-Center, Phase Ib/Ⅱ Clinical Trial of Max-40279-01 in Combination With Azacitidine (AZA) in Adult Patients With Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Trial Snapshot
- Phase
- Phase 1
- Sponsor
- Maxinovel Pty., Ltd.
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Maximum tolerated dose (MTD)
Study Overview
Brief Summary
This study is a phase Ib/II study of Max-40279-01 in combination with Azacitidine (AZA) in patients with Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML). This study include Phase Ib and Phase II study. The phase Ib study is designed to evaluate the safety and tolerability of MAX-40279-01 in combination with Azacitidine (AZA) in patients with Relapsed or Refractory AML. The phase II study is designed to preliminarily assess the efficacy and safety of Max-40279-01 in combination with Azacitidine (AZA) in patients with Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML).
Detailed Description
This is a two-part study comprised of a dose escalation part and a dose expansion part.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Males and/or females over age 18
- •A diagnosis of AML according to the World Health Organization (WHO) 2016 criteria with relapsed or refractory disease and have exhausted, or are ineligible for therapeutic options, or int-risk or high-risk or very high-risk MDS according to revised International Prognostic Scoring System (IPSS-R);
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Expected survival >3 months.
- •No radiotherapy, surgery or hormonal therapy for any kind of within 2 weeks prior to participating in this study. Patients must have fully recovered from the acute toxicities of any prior treatment with any anti-cancer drugs (including hypomethylating agents in MDS patients), radiotherapy or other anti-cancer modalities (i.e., returned to baseline status as noted before most recent treatment) for any tumors. Patients with persisting, stable chronic toxicities from such prior treatment ≤Grade 1 are eligible, but must be documented as such.
- •Signed informed consent form.
Exclusion Criteria
- •Acute promyelocytic leukemia according to World Health Organization 2016 criteria
- •Known central nervous system involvement
- •Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product
- •Known allergies, hypersensitivity, or intolerance to Max-40279-01 or AZA or the excipients of these treatments
- •Previously treated malignancies other than the current disease, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years at the trial entry
Arms & Interventions
Max-40279-01 in combination with Azacitidine (AZA)
This is an open-label Phase Ib/II clinical study. The study will be conducted in two parts:
Part I: Phase Ib dose escalation. Participants receive Max-40279-01 in combination with azacytidine (AZA), with different dose schedules.
Part II: Phase II dose expansion. Participants divide into positive group and negative group according to whether FLT3 gene mutation occurs, approximately 40 people per group.
All participants receive the recommended dose for Part 2 of Max-40279-01 with azacytidine (AZA).
Intervention: MAX-40279-01 (Drug)
Outcomes
Primary Outcomes
Maximum tolerated dose (MTD)
Time Frame: Through study Part 1 completion, an average of 6 months
To explore the maximum tolerable dose (MTD) of Max-40279-01 in combination with Azacitidine (AZA) for patients with r/r AML or MDS, the recommended phase II dose (RP2D).
Rate of complete remission (CRc)
Time Frame: Up to 24 months
including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)
Overall survival(OS)
Time Frame: Up to 24 months
Phase II dose (RP2D)
Time Frame: Through study Part 1 completion, an average of 6 months
Recommended phase II dose (RP2D)
Secondary Outcomes
- Objective response rate (ORR)(1 months (anticipated))
- Cmax(Approximately 4 weeks)
- Tmax(Approximately 4 weeks)
- t1/2(Approximately 4 weeks)
- AUC(Approximately 4 weeks)
- Safety and tolerability assessed by incidence and severity of adverse events(24 months)