Clinical trial NCT05799079: Decitabine and Cedazuridine in Combination With Venetoclax for the Treatment of Patients Who Have Relapsed Acute Myeloid Leukemia After Donor Stem Cell Transplant
Official title: Phase 2 Study of Decitabine and Cedazuridine in Combination With Venetoclax for AML Relapse After Allogeneic Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Acute Myeloid Leukemia
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Comprehensive Cancer Network
name: Taiho Oncology, Inc.
First posted: 2023-04-05
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial tests how well decitabine and cedazuridine (DEC-C) works in combination with venetoclax in treating acute myeloid leukemia (AML) in patients whose AML has come back after a period of improvement (relapse) after a donor stem cell transplant. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving DEC-C in combination with venetoclax may kill more cancer cells in patients with relapsed AML.

Detailed description: PRIMARY OBJECTIVE:

I. To assess the effect of DEC-C/venetoclax on the investigator-assessed composite complete remission (CR) rate (CR/complete remission with partial hematologic recovery \[CRh\]/complete remission with incomplete hematologic recovery \[CRi\]).

SECONDARY OBJECTIVES:

I. To assess the rate of partial response (PR) and morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax. II. To assess the relapse free survival of patients treated with DEC-C/venetoclax.

III. To assess overall survival of patients treated with DEC-C/venetoclax. IV. To assess the safety and tolerability of DEC-C/venetoclax in the post-hematopoietic cell transplant (HCT) setting.

V. To assess the rates of measurable residual disease negativity in patients achieving a CR.

OUTLINE:

Patients receive venetoclax orally (PO) daily for 28 days in a 28-day cycle. Patients receive DEC-C PO daily on days 1-5 of a 28-day cycle. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Eligibility criteria: Inclusion Criteria:

* Age \>= 18 years at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF and meet all study requirements
* History of morphologically confirmed AML (per World Health Organization \[WHO\] diagnostic criteria) with evidence of disease recurrence (\>= 5% blasts consistent with prior disease) that occurs after allogeneic hematopoietic cell transplantation (HCT). Patients transplanted for another indication (e.g., myelodysplastic syndrome/chronic myelomonocytic leukemia \[MDS/CMML\]) who relapse with AML are eligible to enroll
* White blood cells (WBC) must be less than 25,000/ul for at least three days prior to cycle 1, day 1 (C1D1) (hydroxyurea allowed)
* A bone marrow biopsy must be performed and tissue collected for entrance to the trial
* Eastern Cooperative Oncology Group Performance Status of 0 - 2
* Alanine transaminase (ALT) serum glutamic pyruvic transaminase (SGPT) and/or aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 3x upper limit of normal (ULN)
* Total bilirubin \< 1.5 x ULN

  \* Patients with Gilbert's syndrome (hereditary indirect hyperbilirubinemia) must have a total bilirubin of \< 3 x ULN
* Calculated creatinine clearance \>= 30 ml/min (per the Cockroft-Gault formula)
* Willingness to abide by all study requirements, including contraception, maintenance of a pill diary, and acceptance of recommended supportive care medications

Exclusion Criteria:

* Prior relapse or progression while receiving venetoclax or other commercially available or investigational BCL-2 inhibitor
* Anticancer therapy, including investigational agents =\< 2 weeks or =\< 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted)
* Inadequate recovery from toxicity attributed to prior anti-cancer therapy to =\< Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version \[v\]5.0), excluding alopecia or fatigue
* History of allogeneic HCT, or other cellular therapy product, within 3 months of signing consent
* Clinically active acute or chronic graft versus host disease (GVHD). Patients must be off calcineurin inhibitors for at least 4 weeks to be eligible
* Radiation therapy or major surgery within 3 weeks of signing consent
* Active, uncontrolled infection. Patients with infection under active treatment and controlled with antibiotics are eligible. Prophylaxis is acceptable
* Inability to tolerate oral medication, presence of poorly controlled gastrointestinal disease, or dysfunction that could affect study drug absorption
* Active documented central nervous system leukemia
* Concurrent treatment with a non-permitted concomitant medication
* Other malignancy IF currently being treated or likely to be treated in next 6 months except for basal or squamous cell carcinoma of the skin or cervical carcinoma in situ
* Pregnancy or breastfeeding females
* Known chronic alcohol or drug abuse
* Clinically significant cardiovascular disease with major event or cardiac intervention within the past 6 months (e.g. percutaneous intervention, coronary artery bypass graft, documented cardiac heart failure) as determined by the investigator
* Any other condition deemed by the investigator to make the patient a poor candidate for clinical trial and/or treatment with investigational agents

Primary outcomes:
measure: Composite complete response (CR) rate (CR/complete response with partial recovery of peripheral blood counts [CRh]/complete remission with incomplete hematological recovery [CRi])
timeFrame: Up to 24 months post-treatment.
Secondary outcomes:
measure: Rate of partial response (PR) following treatment with DEC-C/venetoclax
timeFrame: Up to 24 months post-treatment.
measure: Rate of morphologic leukemia free state (MLFS) following treatment with DEC-C/venetoclax
timeFrame: Up to 24 months post-treatment.
measure: Rate of relapse free survival
timeFrame: Up to 24 months post-treatment.
measure: Rate of overall survival
timeFrame: Up to 24 months post-treatment.
measure: Incidence of adverse events
timeFrame: Up to 24 months post-treatment.
measure: Rate of measurable residual disease negativity in patients achieving a CR
timeFrame: Up to 24 months post-treatment.
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University/Ingram Cancer Center
name: Sanjay Mohan, MD
role: PRINCIPAL_INVESTIGATOR
References: