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

NCT03969420 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: TPI-ALV-202
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 18

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.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Tolero, Phase 2, AML, Relapsed, Refractory, Alvocidib, Venetoclax

Outcome Measures

Primary Outcomes (1)

• Combined Complete Remission

  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 Outcomes (7)

• Median Overall Survival

  From first dose until disease progression or death; through study termination, an average of 10 months

• Complete Response Rate

  Response assessments were measured from date of first dose through end of treatment date, an average of 3 months

• Composite CR Rate

  Response assessments were measured from date of first dose through end of treatment date, an average of 3 months

• Combined Response Rate

  Response assessments were measured from date of first dose through end of treatment date, an average of 3 months

• Event Free Survival (EFS)

  From first dose until disease progression or death; through study termination, an average of 10 months

Study Arms (4)

Lead-In Cohort: Arm 1

EXPERIMENTAL

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)

Lead-In Cohort: Arm 2

EXPERIMENTAL

Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).

Drug: Alvocidib (flavopiridol)

Stage 1: Arm 1

EXPERIMENTAL

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)

Stage 1: Arm 2

EXPERIMENTAL

Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).

Drug: Alvocidib (flavopiridol)

Interventions

Alvocidib (flavopiridol) and cytarabine (Ara-C) DRUG

Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection

Lead-In Cohort: Arm 1; Stage 1: Arm 1

Alvocidib (flavopiridol) DRUG

Administered intravenously

Lead-In Cohort: Arm 2; Stage 1: Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (18)

Community Medical Providers

Clovis, California, 93611, United States

Location

City of Hope National Medical Center, City of Hope Medical Center

Duarte, California, 91010, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California, San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Advent Health Medical Group Blood & Marrow Transplant at Orlando

Orlando, Florida, 32804, United States

Location

Orlando Health, Inc, Univ of Florida Health Cancer Center

Orlando, Florida, 32806, United States

Location

Indiana Blood and Marrow Translplantation - Clinic

Indianapolis, Indiana, 46237, United States

Location

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87106, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Columbia University Medical Center

New York, New York, 10027, United States

Location

University of North Carolina (UNC)

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Sciences University - Knight Cancer Institute - Center for Hematologic Malignancies

Portland, Oregon, 97239, United States

Location

Allegheny Health Network

Pittsburgh, Pennsylvania, 15212, United States

Location

Baylor University Center

Dallas, Texas, 75211, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

alvocidib; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Reyna Bishop
• Organization: Sumitomo Pharma Oncology, Inc

reyna.bishop@oncology.Sumitomo-Pharma.com

512-363-8755

Study Officials

• Stephen Anthony, DO

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Two-stage

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: May 31, 2019
• Study Start: January 15, 2020
• Primary Completion: April 22, 2021
• Study Completion: May 14, 2021
• Last Updated: November 9, 2023
• Results First Posted: October 19, 2022

Record last verified: 2023-11

Locations

US (18)