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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03969420
Recruitment Status : Not yet recruiting
First Posted : May 31, 2019
Last Update Posted : May 31, 2019
Sponsor:
Information provided by (Responsible Party):
Tolero Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE May 29, 2019
First Posted Date  ICMJE May 31, 2019
Last Update Posted Date May 31, 2019
Estimated Study Start Date  ICMJE September 2019
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
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: 48 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Stage 2 regimen to be selected based on Stage 1 performance. [ Time Frame: 12 months ]
  • Median overall survival. [ Time Frame: 48 months ]
  • CR rate [ Time Frame: 48 months ]
  • Composite CR rate - Combined CR + CRi + CRh (CR + partial recovery of both blood cell types) [ Time Frame: 48 months ]
  • Combined Response Rate - CR + CRi + CRh + MLFS (Morphologic leukemia-free state) + PR (partial response) [ Time Frame: 48 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 [ Time Frame: 24 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 [ Time Frame: 48 months ]
  • Safety and tolerability of the regimen, as determined by analyzing the incidence rates of treatment-emergent adverse events (TEAEs) [ Time Frame: 48 months ]
  • Mortality (all causes) at 30 and 60 days following last treatment [ Time Frame: 48 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, Two-stage
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Myeloid Leukemia (AML)
Intervention  ICMJE
  • Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)
    Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection
  • Drug: Alvocidib (flavopiridol)
    Administered intravenously
Study Arms  ICMJE
  • Experimental: Stage 1: Arm 1
    Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days)
    Intervention: Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)
  • Experimental: Stage 1: Arm 2
    Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days).
    Intervention: Drug: Alvocidib (flavopiridol)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: May 29, 2019)
128
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2023
Estimated Primary Completion Date September 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. Are refractory (i.e., 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 duration ≥90 days) after initial induction therapy with venetoclax in combination with azacytidine or decitabine.
  4. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2.
  5. Have a glomerular filtration rate (GFR) ≥30 mL/min.
  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 a previous treatment with alvocidib or any other CDK inhibitor.
  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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reyna Bishop, MS, RD 512-363-8755 rbishop@toleropharma.com
Contact: Susan Smith, MSN 210-414-7702 su.smith@toleropharma.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03969420
Other Study ID Numbers  ICMJE TPI-ALV-202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tolero Pharmaceuticals, Inc.
Study Sponsor  ICMJE Tolero Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Stephen Anthony, DO Tolero Pharmaceuticals, Inc.
PRS Account Tolero Pharmaceuticals, Inc.
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP