A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Max-40279-01 in Combination With Azacitidine (AZA) in Patients With Myelodysplastic Syndrome (MDS) or Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndrome; Relapsed/Refractory Acute Myeloid Leukemia
• Intervention / Treatment: Drug: MAX-40279-01

Detailed Description

This is a two-part study comprised of a dose escalation part and a dose expansion part.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology & Blood Diseases Hospital
    • Contact: jianxiang Wang; Phone Number: 86-22-23909278; Email: wangjx@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males and/or females over age 18
2. 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);
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
4. Expected survival >3 months.
5. 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.
6. Signed informed consent form.

Exclusion Criteria:

1. Acute promyelocytic leukemia according to World Health Organization 2016 criteria
2. Known central nervous system involvement
3. Medical history of difficulty swallowing, malabsorption or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested product
4. Known allergies, hypersensitivity, or intolerance to Max-40279-01 or AZA or the excipients of these treatments
5. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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).

Drug: MAX-40279-01; Drug: AZA AZA will be administered at 75 mg/m^2 by subcutaneous injection for 7 consecutive days from D1 to D7 in 28-day treatment cycles. Other Name: Azacitidine Drug: Max-40279-01 Max-40279-01 will be administered as a combination of multiple oral capsules containing 5 and 25 mg. An alternate combination of 35 mg, 50 mg and 60 mg Max-40279-01 twice a day may be utilized. Other Name: NA; Other Names: Azacitidine (AZA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	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).	Through study Part 1 completion, an average of 6 months
Phase II dose (RP2D)	Recommended phase II dose (RP2D)	Through study Part 1 completion, an average of 6 months
Overall survival(OS)		Up to 24 months
Rate of complete remission (CRc)	including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time to maximum plasma concentration	Approximately 4 weeks
AUC	Area under the time-concentration curve	Approximately 4 weeks
t1/2	Observed terminal half-life	Approximately 4 weeks
Cmax	Maximum plasma drug concentration	Approximately 4 weeks
Objective response rate (ORR)	The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on IRWG.	1 months (anticipated)
Safety and tolerability assessed by incidence and severity of adverse events	All grade ≥ 3 toxicities according to CTCAE (Common Terminology Criteria for Adverse Events) version 5 will be tabulated	24 months

Collaborators and Investigators

• Sponsor: Maxinovel Pty., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 16, 2021
• Primary Completion (ANTICIPATED): April 30, 2022
• Study Completion (ANTICIPATED): October 31, 2022

Study Registration Dates

• First Submitted: September 18, 2021
• First Submitted That Met QC Criteria: September 18, 2021
• First Posted (ACTUAL): September 29, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndrome; Relapsed/Refractory Acute Myeloid Leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: MAX-40279-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No