Recurrent Acute Myeloid Leukemia
Conditions
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.
Interventions
DRUGVenetoclax
Given by mouth
DRUGDecitabine
Given by mouth
DRUGCedazuridine
Given by mouth
PROCEDUREBone Marrow Aspiration and Biopsy
Undergo bone marrow biopsy
PROCEDUREBiospecimen Collection
Undergo blood sample collection
Sponsors
National Comprehensive Cancer Network
Taiho Oncology, Inc.
Sanjay Mohan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants That Achieved a Complete Response to Therapy | 9 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Morphologic Leukemia Free State (MLFS) Following Treatment With DEC-C/Venetoclax | Up to 24 months post-treatment. | — |
| Rate of Relapse Free Survival | Up to 24 months post-treatment. | Relapse free survival was estimated by the Kaplan-Meier Method |
| Number of Participants That Achieved a Partial Response to Therapy | 9 months | — |
| Number of Treatment-related Adverse Events | The one patient that was enrolled on the study was on treatment for 3 months and adverse event data were followed during treatment and 35 days after completing treatment. | List of adverse events that were attributed as related to study treatment is reported. All occurrences of a particular adverse event is reported. |
| Rate of Measurable Residual Disease Negativity in Patients Achieving a CR | Up to 24 months post-treatment. | — |
| Rate of Overall Survival | Up to 24 months post-treatment. | Overall survival was estimated using the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 DEC-C 100mg/35mg D1-5 Venetoclax 400 mg per day (continuous) | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Dose Level 1 |
|---|---|
| Age, Continuous | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Number of Participants That Achieved a Complete Response to Therapy
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | Number of Participants That Achieved a Complete Response to Therapy | 0 Participants |
Secondary
Number of Participants That Achieved a Partial Response to Therapy
Time frame: 9 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Level 1 | Number of Participants That Achieved a Partial Response to Therapy | 0 Participants |
Secondary
Number of Treatment-related Adverse Events
List of adverse events that were attributed as related to study treatment is reported. All occurrences of a particular adverse event is reported.
Time frame: The one patient that was enrolled on the study was on treatment for 3 months and adverse event data were followed during treatment and 35 days after completing treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | Number of Treatment-related Adverse Events | 5 adverse events of dehydration |
Secondary
Rate of Measurable Residual Disease Negativity in Patients Achieving a CR
Time frame: Up to 24 months post-treatment.
Population: Data not collected for this outcome measure as study was terminated early.
Secondary
Rate of Morphologic Leukemia Free State (MLFS) Following Treatment With DEC-C/Venetoclax
Time frame: Up to 24 months post-treatment.
Population: Data not collected for this outcome measure as study was terminated early.
Secondary
Rate of Overall Survival
Overall survival was estimated using the Kaplan-Meier method.
Time frame: Up to 24 months post-treatment.
Population: Data not collected for this outcome measure as study was terminated early.
Secondary
Rate of Relapse Free Survival
Relapse free survival was estimated by the Kaplan-Meier Method
Time frame: Up to 24 months post-treatment.
Population: Data not collected for this outcome measure as study was terminated early.