Clinical Trials /

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

NCT03969420

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy
  • 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 IDs

  • ORG STUDY ID: TPI-ALV-202
  • NCT ID: NCT03969420

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
Alvocidib (flavopiridol) and cytarabine (Ara-C)Stage 1: Arm 1
Alvocidib (flavopiridol)Stage 1: Arm 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Stage 1: Arm 1ExperimentalRefractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
  • Alvocidib (flavopiridol) and cytarabine (Ara-C)
Stage 1: Arm 2ExperimentalRelapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
  • Alvocidib (flavopiridol)

Eligibility Criteria

        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 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 3 weeks (with the exception of
             hydroxyurea or if the patient has definite refractory disease). Refractory patients
             who received therapy within the last 3 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Time Frame:18 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Median overall survival.
Time Frame:42 months
Safety Issue:
Description:
Measure:CR rate
Time Frame:18 months
Safety Issue:
Description:
Measure:Composite CR rate - Combined CR + CRi + CRh (CR + partial recovery of both blood cell types)
Time Frame:18 months
Safety Issue:
Description:
Measure:Combined Response Rate - CR + CRi + CRh + MLFS (Morphologic leukemia-free state) + PR (partial response)
Time Frame:18 months
Safety Issue:
Description:
Measure: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
Time Frame:42 months
Safety Issue:
Description:
Measure:Duration of composite CR, defined as the time from first documented response of CR, CRi or CRhi to relapse or death from any cause
Time Frame:18 months
Safety Issue:
Description:
Measure: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
Time Frame:44 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sumitomo Dainippon Pharma Oncology, Inc

Trial Keywords

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

Last Updated

July 9, 2020