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

NCT ID: NCT06536959

Last Updated: 2024-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-18
• Study Completion Date: 2027-07-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VA-PD1i

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

Group Type: EXPERIMENTAL

PD-1 inhibitor, Venetoclax, Decitabine, Azacytidine

Intervention Type: 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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

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

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiao-Ning Gao

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Xiao-ning Gao

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Xiao-ning Gao

Role: primary

gaoxn@263.net

86-010-66947169

Lei Xu

Role: backup

xulei800@hotmail.com

86-010-66947174

Other Identifiers

VA-PD1-MN

Identifier Type: -

Identifier Source: org_study_id