VA Combined With PD-1 Inhibitor for the Treatment of Relapsed and Refractory AML and High-risk MDS

A Study of VA Combined With PD-1 Inhibitor in the Treatment of Relapsed and Refractory AML and High-risk MDS

The efficiency and safety of PD-1 inhibitor in combination with venetoclax and hypomethylation agent in relapsed/refractory acute myeloid leukemia or high-risk myelodysplastic syndrome remain uncertain. In this study, the investigators aimed to assess safety and response to a new PD-1 inhibitor-based triple-drug combination regimen (venetoclax + hypomethylation agent + PD-1 inhibitor) in relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome patients, or who had positive minimal residual disease.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Refractory Acute Myeloid Leukemia; Minimal Residual Disease; Relapsed Acute Myeloid Leukemia
• Intervention / Treatment: Drug: PD-1 inhibitor, Venetoclax, Decitabine, Azacytidine

• Study Type: Interventional
• Enrollment (Estimated): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Recruiting
      • Xiao-ning Gao
      • Contact: Xiao-ning Gao; Phone Number: 86-010-66947169; Email: gaoxn@263.net
      • Contact: Lei Xu; Phone Number: 86-010-66947174; Email: xulei800@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with relapsed and refractory acute myeloid leukemia (AML) and patients diagnosed with myelodysplastic syndrome (MDS) who require chemotherapy treatment.
• Patients who did not respond or had disease recurrence after 1 course of induction chemotherapy or had positive immune residues after induction chemotherapy or positive molecular residues (if any) after induction chemotherapy.
• Voluntarily participate in clinical research and sign an informed consent form and be willing to follow and be able to complete all experimental procedures.
• The toxic and side effects caused by the last treatment should be recovered.
• Eastern Cooperative Oncology Group score of 0 to 3 points.

• The organ function is intact.

  • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2×ULN (Upper Limit of Normal).
  • Creatinine≤2×ULN.
  • Bilirubin≤2×ULN.
• Karnofsky≥70.
• The expected survival period is at least 12 weeks.
• Non-pregnant, non-breastfeeding women.

Exclusion Criteria:

• Suffering from other untreated or unrelieved malignant tumors within 2 years.
• Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, and experimental therapy were performed within 2 weeks of the first medication.
• Suffering from any other known serious and/or uncontrolled disease (eg, uncontrolled diabetes; cardiovascular disease, including congestive heart failure New York Heart Association [NYHA] Class III or IV, 6 months patients with myocardial infarction and poorly controlled blood pressure); chronic renal failure; or active uncontrolled infection); the investigators considered unsuitable for this clinical trial.
• Patients who are unwilling or unable to comply with the protocol.
• Currently being treated with other systemic anti-tumor or anti-tumor research drugs.
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VA-PD1i; Patients are treated with PD-1 inhibitor combined with venetoclax and decitabine/azacytidine.

Drug: PD-1 inhibitor, Venetoclax, Decitabine, Azacytidine; For AML patients: PD-1 inhibitor was given at a dose of 200mg on day 21 of the treatment. Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days or azacytidine was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. For MDS patients: PD-1 inhibitor was given at a dose of 200mg on day 21 of the treatment. Venetoclax was given at a dose of 400 mg/day for 14 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days or azacytidine was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. The venetoclax starting dose is 100 mg on the first day, ramping up to 200 mg on the second day and finally 400 mg once daily. The steady daily dose (after ramp-up phase) should be reduced to 100 mg (coadministered with moderate CYP3A inhibitors or P-gp inhibitors) and 70 mg (coadministered with strong CYP3A4 inhibitors).; Other Names: Venetoclax (ABT-199, GDC-0199); Decitabine (Dacogen, 5-aza-2-deoxycytidine); Azacitidine (5-Azacytidine, Ladakamycin); PD-1 inhibitor (Tislelizumab)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)	At the end of Cycle 2 (each cycle is 28 days)
Complete minimal residual disease (MRD) Response Rate	Percentage of subjects with MRD negative or MRD < 0.01%	At the end of Cycle 2 (each cycle is 28 days)
MRD Response Rate	Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry	At the end of Cycle 2 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-Free Survival	Time interval from leukemia free state to the first recurrence or death	24 months
Overall Survival	Time interval from start of treatment until death or last follow-up	24 months
Duration of response	Time interval from morphologic/MRD response to loss of response or death	24 months
Adverse events	Number of subjects with adverse events	start of treatment to 2 weeks after end of treatment

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Estimated): August 5, 2024

Study Record Updates

• Last Update Posted (Estimated): August 5, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Venetoclax; PD-1 inhibitor; Hypomethylation agen
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Neoplastic Processes; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm, Residual; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Decitabine; Venetoclax; Azacitidine; Immune Checkpoint Inhibitors; Tislelizumab
• Other Study ID Numbers: VA-PD1-MN

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
• product manufactured in and exported from the U.S.: No