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NCT Number: NCT06536959

VA Combined With PD-1 Inhibitor for 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.

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Key information

Conditions

Relapsed Acute Myeloid Leukemia Bone Marrow Diseases Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Minimal Residual Disease Myelodysplastic Syndromes Neoplasm, Residual Neoplasms Neoplasms by Histologic Type Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms Refractory Acute Myeloid Leukemia

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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).

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

Primary outcomes

  1. Complete remission rate

    Time frame: At the end of Cycle 2 (each cycle is 28 days)

    percentage of subjects with complete remission (CR) and incomplete hematologic recovery (CRi)

  2. Complete minimal residual disease (MRD) Response Rate

    Time frame: At the end of Cycle 2 (each cycle is 28 days)

    Percentage of subjects with MRD negative or MRD < 0.01%

  3. MRD Response Rate

    Time frame: At the end of Cycle 2 (each cycle is 28 days)

    Percentage of subjects with MRD < 0.1% detectable by multicolor flow cytometry

Secondary outcomes

  1. Relapse-Free Survival

    Time frame: 24 months

    Time interval from leukemia free state to the first recurrence or death

  2. Overall Survival

    Time frame: 24 months

    Time interval from start of treatment until death or last follow-up

  3. Duration of response

    Time frame: 24 months

    Time interval from morphologic/MRD response to loss of response or death

  4. Adverse events

    Time frame: start of treatment to 2 weeks after end of treatment

    Number of subjects with adverse events

Sponsors and collaborators

Lead sponsor

Beijing 302 Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Aug 5, 2024
Registry last updated
Aug 5, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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