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

Sponsor

Sumitomo Pharma Oncology, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT03969420

Collaborator

(none)

Enrollment

Locations

Arms

15.9

Actual Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML)	Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C) Drug: Alvocidib (flavopiridol)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, Two-stageRandomized, Two-stage

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 15, 2020

Actual Primary Completion Date :

Apr 22, 2021

Actual Study Completion Date :

May 14, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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) [18 months]

Secondary Outcome Measures

Median overall survival. [42 months]
CR rate [18 months]
Composite CR rate - Combined CR + CRi + CRh (CR + partial recovery of both blood cell types) [18 months]
Combined Response Rate - CR + CRi + CRh + MLFS (Morphologic leukemia-free state) + PR (partial response) [18 months]
EFS (Event-free survival) defined as the time from first treatment (Day 1) until (a) treatment failure, (b) relapse after CR, /CRi, or CRh or (c) death from any cause, whichever occurs first, censored at 2 years [42 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 [18 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 [44 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

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