Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy
Condition: Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Alvocidib (flavopiridol) and cytarabine (Ara-C); Alvocidib (flavopiridol)
Intervention description: Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection; Administered intravenously
Intervention MeSH terms: Cytarabine; Alvocidib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Two-stage
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Tolero, Phase 2, AML, Relapsed, Refractory, Alvocidib, Venetoclax

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.
    

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 (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.