Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy
- Conditions
- Acute Myeloid Leukemia (AML)
- Interventions
- Registration Number
- NCT03969420
- Lead Sponsor
- Sumitomo Pharma America, Inc.
- Brief Summary
This study will evaluate the safety and efficacy of alvocidib in patients with AML who have either relapsed from or are refractory to venetoclax in combination with azacytidine or decitabine.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
- Be ≥18 years of age.
- Have an established, pathologically confirmed diagnosis of AML by World Health Organization (WHO) criteria, excluding acute promyelocytic leukemia (APL-M3) with a bone marrow of >5% blasts based on histology or flow cytometry.
- Have received initial induction therapy with venetoclax in combination with azacytidine or decitabine (with or without other investigational agents as part of a clinical trial; requires Medical Monitor review) and were either refractory (failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) or have relapsed (reoccurrence of disease following a CR/CRi with duration ≥90 days).
- Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
- Have a glomerular filtration rate (GFR) ≥30 mL/min using the Cockcroft-Gault equation.
- Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN).
- Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia).
- Be infertile or agree to use an adequate method of contraception:sexually active patients and their partners must use an effective method of contraception associated with a low failure rate prior to study entry, for the duration of study participation, and for at least 3 months (males) and 6 months (females) after the last dose of study drug.
- Be able to comply with the requirements of the entire study.
- Provide written informed consent prior to any study related procedure: in the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.
- Received any previous treatment with alvocidib or any other CDK inhibitor or received prior anti-leukemic therapy other than first-line venetoclax in combination with azacytidine or decitabine.
- Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting treatment on either arm.
- Received an allogeneic stem cell transplant within 60 days of the start of study treatment. Patients who received an allogeneic stem cell transplant must be off all immunosuppressants at the time of study treatment
- Are receiving or have received systemic therapy for graft-versus-host disease.
- Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #2 above).
- Received antileukemic therapy within the last 2 weeks or 3-5 half lives of the prior therapy (with the exception of hydroxyurea or if the patient has definite refractory disease), whichever is less. Refractory patients who received therapy within the last 2 weeks may be eligible with prior approval of the Medical Monitor.
- Diagnosed with acute promyelocytic leukemia (APL-M3).
- Have active central nervous system (CNS) leukemia.
- Have evidence of uncontrolled disseminated intravascular coagulation.
- Have an active, uncontrolled infection.
- Have other life-threatening illness.
- Have other active malignancies requiring treatment or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia.
- Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
- Are pregnant and/or nursing.
- Have received any live vaccine within 14 days prior to first study drug administration.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1: Arm 1 Alvocidib (flavopiridol) and cytarabine (Ara-C) Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration \<90 days) Stage 1: Arm 2 Alvocidib (flavopiridol) Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days). Lead-In Cohort: Arm 1 Alvocidib (flavopiridol) and cytarabine (Ara-C) Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration \<90 days) Lead-In Cohort: Arm 2 Alvocidib (flavopiridol) Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
- Primary Outcome Measures
Name Time Method Combined Complete Remission Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months. Rate of combined complete remission (complete remission (CR) + CR with incomplete hematological recovery (CRi)), as defined by the International Working Group Criteria and 2017 European LeukemiaNet).
Combined complete remissions (patients with a best response of CR or CRi), complete remissions, composite complete remissions (patients with a best response of CR, CRi or CRh), and combined responses (patients with a best response of CR, CRi, CRh, MLFS or PR) will be summarized by observed response rates and estimated 95% CIs.
- Secondary Outcome Measures
Name Time Method Complete Response Rate Response assessments were measured from date of first dose through end of treatment date, an average of 3 months Percentage of patients achieving complete response (CR) whose bone marrow is determined to be negative for minimal residual disease (MRD) using standardized techniques (ie, multiparametric flow cytometry \[MPFC\] and molecular testing including next generation sequencing \[NGS\]
Composite CR Rate Response assessments were measured from date of first dose through end of treatment date, an average of 3 months Patients with a best response of CR + CRi + CRh (CR + partial recovery of both blood cell types)
Combined Response Rate Response assessments were measured from date of first dose through end of treatment date, an average of 3 months Combined Percentage of Patients Achieving One of the Following: CR \< CRi, CRh, MLFS, PR
Morphologic leukemia-free state (MLFS) = Bone marrow blasts \<5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required;
Partial Response (PR) = Meets all hematologic values required for CR but with a decrease of at least 50% in the percentage of blasts to ≥5% to ≤25% in bone marrowTransfusion Independence Transfusion dependence was measured from 28 days prior to first dose through 56 days after last dose, an average of 6 months Rates of 28- and 56-day Transfusion Independence (TI) = Percentages of patients who do not receive red blood cell (RBC) transfusions, platelet (PLT) transfusions, and neither RBC nor PLT transfusions for 28 and 56 days; comprised of 6 secondary endpoints
Median Overall Survival From first dose until disease progression or death; through study termination, an average of 10 months Time from treatment (Day 1) until death from any cause
Event Free Survival (EFS) From first dose until disease progression or death; through study termination, an average of 10 months Event Free Survival - time from first treatment (D1) until (a) treatment failure, (b) relapse after CR/Cri or CRh, or (c) death from any cause, whichever occurs first
Duration of Composite Complete Remission (CR) Response assessments were measured from date of first dose through end of treatment date, an average of 3 months Duration of Composite CR, defined as the time from first documented response of CR, CRi or CRhi to relapse or death from any cause
Trial Locations
- Locations (18)
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Orlando Health, Inc, Univ of Florida Health Cancer Center
🇺🇸Orlando, Florida, United States
Baylor University Center
🇺🇸Dallas, Texas, United States
Advent Health Medical Group Blood & Marrow Transplant at Orlando
🇺🇸Orlando, Florida, United States
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
City of Hope National Medical Center, City of Hope Medical Center
🇺🇸Duarte, California, United States
Community Medical Providers
🇺🇸Clovis, California, United States
Indiana Blood and Marrow Translplantation - Clinic
🇺🇸Indianapolis, Indiana, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of North Carolina (UNC)
🇺🇸Chapel Hill, North Carolina, United States
Allegheny Health Network
🇺🇸Pittsburgh, Pennsylvania, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of California, San Francisco Medical Center
🇺🇸San Francisco, California, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Oregon Health & Sciences University - Knight Cancer Institute - Center for Hematologic Malignancies
🇺🇸Portland, Oregon, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
University of Kansas Medical Center
🇺🇸Westwood, Kansas, United States