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)

Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05061147
• Other study ID #: MAX-40279-004
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 16, 2021
• Est. completion date: October 31, 2022

Study information

• Verified date: September 2021
• Source: Maxinovel Pty., Ltd.
• Contact: Hanying Bao, MD,Ph.D
• Phone: +86-021-51370693
• Email: hybao[@]maxinovel.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: October 31, 2022
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Relapsed/Refractory Acute Myeloid Leukemia
• Syndrome

Intervention

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

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Maxinovel Pty., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase II dose (RP2D)	Recommended phase II dose (RP2D)	Through study Part 1 completion, an average of 6 months
Primary	Overall survival(OS)		Up to 24 months
Primary	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	Tmax	Time to maximum plasma concentration	Approximately 4 weeks
Secondary	Cmax	Maximum plasma drug concentration	Approximately 4 weeks
Secondary	AUC	Area under the time-concentration curve	Approximately 4 weeks
Secondary	t1/2	Observed terminal half-life	Approximately 4 weeks
Secondary	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)
Secondary	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