Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy

November 7, 2023 updated by: Sumitomo Pharma America, Inc.

A Phase 2, Open-label, Randomized, Two-stage Clinical Study of Alvocidib in Patients With Relapsed/Refractory Acute Myeloid Leukemia Following Treatment With Venetoclax Combination Therapy

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Clovis, California, United States, 93611
        • Community Medical Providers
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center, City of Hope Medical Center
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center
      • San Francisco, California, United States, 94143
        • University of California, San Francisco Medical Center
    • Florida
      • Orlando, Florida, United States, 32804
        • Advent Health Medical Group Blood & Marrow Transplant at Orlando
      • Orlando, Florida, United States, 32806
        • Orlando Health, Inc, Univ of Florida Health Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46237
        • Indiana Blood and Marrow Translplantation - Clinic
    • Kansas
      • Westwood, Kansas, United States, 66205
        • University of Kansas Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10027
        • Columbia University Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina (UNC)
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health & Sciences University - Knight Cancer Institute - Center for Hematologic Malignancies
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny Health Network
    • Texas
      • Dallas, Texas, United States, 75211
        • Baylor University Center
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Be ≥18 years of age.
  2. 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.
  3. 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).
  4. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
  5. Have a glomerular filtration rate (GFR) ≥30 mL/min using the Cockcroft-Gault equation.
  6. Have an alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≤5 times upper limit of normal (ULN).
  7. Have a total bilirubin level ≤2.0 mg/dL (unless secondary to Gilbert syndrome, hemolysis, or leukemia).
  8. 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.
  9. Be able to comply with the requirements of the entire study.
  10. 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.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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
  4. Are receiving or have received systemic therapy for graft-versus-host disease.
  5. Have a peripheral blast count of >30,000/mm3 (may use hydroxyurea as in #2 above).
  6. 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.
  7. Diagnosed with acute promyelocytic leukemia (APL-M3).
  8. Have active central nervous system (CNS) leukemia.
  9. Have evidence of uncontrolled disseminated intravascular coagulation.
  10. Have an active, uncontrolled infection.
  11. Have other life-threatening illness.
  12. Have other active malignancies requiring treatment or diagnosed with other malignancies within the last 6 months, except nonmelanoma skin cancer or cervical intraepithelial neoplasia.
  13. Have mental deficits and/or psychiatric history that may compromise the ability to give written informed consent or to comply with the study protocol.
  14. Are pregnant and/or nursing.
  15. Have received any live vaccine within 14 days prior to first study drug administration.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lead-In Cohort: Arm 1
Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)
Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection
Experimental: Lead-In Cohort: Arm 2
Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
Drug: Alvocidib (flavopiridol)
Administered intravenously
Experimental: Stage 1: Arm 1
Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)
Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection
Experimental: Stage 1: Arm 2
Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
Drug: Alvocidib (flavopiridol)
Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Combined Complete Remission
Time Frame: 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.
Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Overall Survival
Time Frame: 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
From first dose until disease progression or death; through study termination, an average of 10 months
Complete Response Rate
Time Frame: 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]
Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Composite CR Rate
Time Frame: 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)
Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Combined Response Rate
Time Frame: 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 marrow
Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Event Free Survival (EFS)
Time Frame: 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
From first dose until disease progression or death; through study termination, an average of 10 months
Duration of Composite Complete Remission (CR)
Time Frame: 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
Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Transfusion Independence
Time Frame: 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
Transfusion dependence was measured from 28 days prior to first dose through 56 days after last dose, an average of 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sumitomo Pharma America, Inc.

Investigators

  • Study Director: Stephen Anthony, DO, Sumitomo Pharma America, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2020

Primary Completion (Actual)

April 22, 2021

Study Completion (Actual)

May 14, 2021

Study Registration Dates

First Submitted

May 29, 2019

First Submitted That Met QC Criteria

May 29, 2019

First Posted (Actual)

May 31, 2019

Study Record Updates

Last Update Posted (Estimated)

November 9, 2023

Last Update Submitted That Met QC Criteria

November 7, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TPI-ALV-202

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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