Back to resultsA 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)
Primary Purpose
Leukemia, Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia
Status
Unknown status
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
MAX-40279-01
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia focused on measuring Relapsed/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome
Eligibility Criteria
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 0-2.
- 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
Sites / Locations
- Institute of Hematology & Blood Diseases HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Max-40279-01 in combination with Azacitidine (AZA)
Arm Description
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).
Outcomes
Primary Outcome Measures
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).
Phase II dose (RP2D)
Recommended phase II dose (RP2D)
Overall survival(OS)
Rate of complete remission (CRc)
including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)
Secondary Outcome Measures
Tmax
Time to maximum plasma concentration
Cmax
Maximum plasma drug concentration
AUC
Area under the time-concentration curve
t1/2
Observed terminal half-life
Objective response rate (ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on IRWG.
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
Full Information
NCT ID
NCT05061147
First Posted
September 18, 2021
Last Updated
September 29, 2021
Sponsor
Maxinovel Pty., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05061147
Brief Title
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)
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
September 16, 2021 (Actual)
Primary Completion Date
April 30, 2022 (Anticipated)
Study Completion Date
October 31, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maxinovel Pty., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Myeloid Leukemia, Relapsed/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome
Keywords
Relapsed/Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Max-40279-01 in combination with Azacitidine (AZA)
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
MAX-40279-01
Other Intervention Name(s)
Azacitidine (AZA)
Intervention Description
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
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD)
Description
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).
Time Frame
Through study Part 1 completion, an average of 6 months
Title
Phase II dose (RP2D)
Description
Recommended phase II dose (RP2D)
Time Frame
Through study Part 1 completion, an average of 6 months
Title
Overall survival(OS)
Time Frame
Up to 24 months
Title
Rate of complete remission (CRc)
Description
including Complete Remission with incomplete Platelet recovery (CRp) and Complete Remission with incomplete hematologic recovery (CRi)
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Tmax
Description
Time to maximum plasma concentration
Time Frame
Approximately 4 weeks
Title
Cmax
Description
Maximum plasma drug concentration
Time Frame
Approximately 4 weeks
Title
AUC
Description
Area under the time-concentration curve
Time Frame
Approximately 4 weeks
Title
t1/2
Description
Observed terminal half-life
Time Frame
Approximately 4 weeks
Title
Objective response rate (ORR)
Description
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on IRWG.
Time Frame
1 months (anticipated)
Title
Safety and tolerability assessed by incidence and severity of adverse events
Description
All grade ≥ 3 toxicities according to CTCAE (Common Terminology Criteria for Adverse Events) version 5 will be tabulated
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 0-2.
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hanying Bao, MD,Ph.D
Phone
+86-021-51370693
Email
hybao@maxinovel.com
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
jianxiang Wang
Phone
86-22-23909278
Email
wangjx@ihcams.ac.cn
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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)
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