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

NCT06536959 | Recruiting Phase 2 DMC

• 1 other identifier: VA-PD1-MN
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Myelodysplastic Syndromes; Minimal Residual Disease

Keywords

Venetoclax; Hypomethylation agen; PD-1 inhibitor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Relapse-Free Survival

  24 months

• Overall Survival

  24 months

• Duration of response

  24 months

• Adverse events

  start of treatment to 2 weeks after end of treatment

Study Arms (1)

VA-PD1i

EXPERIMENTAL

Patients are treated with PD-1 inhibitor combined with venetoclax and decitabine/azacytidine.

Drug: PD-1 inhibitor, Venetoclax, Decitabine, Azacytidine

Interventions

PD-1 inhibitor, Venetoclax, Decitabine, Azacytidine DRUG

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).

Also known as: PD-1 inhibitor (Tislelizumab), Venetoclax (ABT-199, GDC-0199), Decitabine (Dacogen, 5-aza-2-deoxycytidine), Azacitidine (5-Azacytidine, Ladakamycin)

VA-PD1i

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing 302 Hospital: lead

Study Sites (1)

Xiao-ning Gao

Beijing, Beijing Municipality, 100071, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasm, Residual

Interventions

Immune Checkpoint Inhibitors; venetoclax; Decitabine; Azacitidine; tislelizumab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: July 31, 2024
• First Posted: August 5, 2024
• Study Start: July 18, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 5, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)