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

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03969420
• Other study ID #: TPI-ALV-202
• Status: Terminated
• Phase: Phase 2
• Start date: January 15, 2020
• Est. completion date: May 14, 2021

Study information

• Verified date: November 2023
• Source: Sumitomo Pharma America, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: May 14, 2021
• Est. primary completion date: April 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Alvocidib (flavopiridol) and cytarabine (Ara-C)
Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection
• Alvocidib (flavopiridol)
Administered intravenously

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina (UNC)	Chapel Hill	North Carolina
United States	Community Medical Providers	Clovis	California
United States	Ohio State University	Columbus	Ohio
United States	Baylor University Center	Dallas	Texas
United States	City of Hope National Medical Center, City of Hope Medical Center	Duarte	California
United States	Indiana Blood and Marrow Translplantation - Clinic	Indianapolis	Indiana
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Advent Health Medical Group Blood & Marrow Transplant at Orlando	Orlando	Florida
United States	Orlando Health, Inc, Univ of Florida Health Cancer Center	Orlando	Florida
United States	Allegheny Health Network	Pittsburgh	Pennsylvania
United States	Oregon Health & Sciences University - Knight Cancer Institute - Center for Hematologic Malignancies	Portland	Oregon
United States	University of California, San Francisco Medical Center	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	University of Kansas Medical Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sumitomo Pharma America, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Median Overall Survival	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
Secondary	Complete Response Rate	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
Secondary	Composite CR Rate	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
Secondary	Combined Response Rate	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
Secondary	Event Free Survival (EFS)	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
Secondary	Duration of Composite Complete Remission (CR)	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
Secondary	Transfusion Independence	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