Acute Myeloid Leukemia (AML)Phase 2NCT03969420
Study of Alvocidib in Patients With Relapsed/Refractory AML Following Treatment With Venetoclax Combination Therapy
A Phase 2 study testing Alvocidib (flavopiridol) and cytarabine (Ara-C) and Alvocidib (flavopiridol) in people with Acute Myeloid Leukemia (AML), run by Sumitomo Pharma America, Inc. at 18 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML)
- What is being tested?
- Alvocidib (flavopiridol) and cytarabine (Ara-C) and Alvocidib (flavopiridol)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 18 sitesUnited States
- Study dates
- 15 Jan 2020to 14 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
University of New Mexico
Albuquerque, New Mexico, 87106
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of North Carolina (UNC)
Chapel Hill, North Carolina, 27599
Community Medical Providers
Clovis, California, 93611
Ohio State University
Columbus, Ohio, 43210
Baylor University Center
Dallas, Texas, 75211
City of Hope National Medical Center, City of Hope Medical Center
Duarte, California, 91010
Indiana Blood and Marrow Translplantation - Clinic
Indianapolis, Indiana, 46237
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
Ochsner Medical Center
New Orleans, Louisiana, 70121
Columbia University Medical Center
New York, New York, 10027
Advent Health Medical Group Blood & Marrow Transplant at Orlando
Orlando, Florida, 32804
Orlando Health, Inc, Univ of Florida Health Cancer Center
Orlando, Florida, 32806
Allegheny Health Network
Pittsburgh, Pennsylvania, 15212
Oregon Health & Sciences University - Knight Cancer Institute - Center for Hematologic Malignancies
Portland, Oregon, 97239
University of California, San Francisco Medical Center
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
University of Kansas Medical Center
Westwood, Kansas, 66205
About this study
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
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.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- Alvocidib (flavopiridol) and cytarabine (Ara-C), Alvocidib (flavopiridol)
- Keywords
- Tolero, Phase 2, AML, Relapsed, Refractory, Alvocidib, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alvocidib (flavopiridol) and cytarabine (Ara-C)Drug
Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection
Alvocidib (flavopiridol)Drug
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Lead-In Cohort: Arm 1 | Experimental | Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) Receives: Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C) |
| Lead-In Cohort: Arm 2 | Experimental | Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days). Receives: Drug: Alvocidib (flavopiridol) |
| Stage 1: Arm 1 | Experimental | Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) Receives: Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C) |
| Stage 1: Arm 2 | Experimental | Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days). Receives: Drug: Alvocidib (flavopiridol) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months.
Secondary outcomes (7)
Median Overall Survival
Time from treatment (Day 1) until death from any cause
Measured: From first dose until disease progression or death; through study termination, an average of 10 months
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]
Measured: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Composite CR Rate
Patients with a best response of CR + CRi + CRh (CR + partial recovery of both blood cell types)
Measured: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
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
Measured: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
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
Measured: From first dose until disease progression or death; through study termination, an average of 10 months
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
Measured: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
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
Measured: Transfusion dependence was measured from 28 days prior to first dose through 56 days after last dose, an average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study start15 Jan 2020
- Primary completion22 Apr 2021
- Study completion14 May 2021
Why it stopped: Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Two-stage
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sumitomo Pharma America, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Anthony, DO, Study director, Sumitomo Pharma America, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03969420
- Sponsor's protocol ID
- TPI-ALV-202
- Status last verified
- Nov 2023
- First submitted
- 29 May 2019
- Last updated
- 9 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03969420
- Acronym / sponsor ID
- TPI-ALV-202
- Conditions
- Acute Myeloid Leukemia (AML)
- Keywords
- Tolero, Phase 2, AML, Relapsed, Refractory, Alvocidib, Venetoclax
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business decision to terminate the development of alvocidib program on 17 November 2020. Patients permitted on treatment until April 22, 2021. The last end-of-treatment follow-up completed on May 14, 2021.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Sumitomo Pharma America, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 22 Apr 2021 (actual)
- Study completion
- 14 May 2021 (actual)
- First posted
- 31 May 2019 (actual)
- Results
- Posted 19 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Randomized, Two-stage
| Arm | Type | Receives |
|---|---|---|
| Lead-In Cohort: Arm 1 | Experimental | Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) |
| Lead-In Cohort: Arm 2 | Experimental | Drug: Alvocidib (flavopiridol)Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days). |
| Stage 1: Arm 1 | Experimental | Drug: Alvocidib (flavopiridol) and cytarabine (Ara-C)Refractory (i.e., failed to achieve a CR/CRi or achieved a CR/CRi with duration <90 days) |
| Stage 1: Arm 2 | Experimental | Drug: Alvocidib (flavopiridol)Relapsed (i.e., reoccurrence of disease following a CR/CRi with duration ≥90 days). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (15 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Alvocidib (flavopiridol) and cytarabine (Ara-C)Alvocidib (flavopiridol), administered intravenously, + cytarabine (Ara-C), administered by subcutaneous injection | Drug | Lead-In Cohort: Arm 1, Stage 1: Arm 1 |
| Alvocidib (flavopiridol)Administered intravenously | Drug | Lead-In Cohort: Arm 2, Stage 1: Arm 2 |
Primary outcome
Combined Complete Remission
Time frame: Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months.
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.
7 secondary outcomes
Median Overall Survival
Time frame: From first dose until disease progression or death; through study termination, an average of 10 months
Complete Response Rate
Time frame: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Composite CR Rate
Time frame: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Combined Response Rate
Time frame: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Event Free Survival (EFS)
Time frame: From first dose until disease progression or death; through study termination, an average of 10 months
Duration of Composite Complete Remission (CR)
Time frame: Response assessments were measured from date of first dose through end of treatment date, an average of 3 months
Transfusion Independence
Time frame: Transfusion dependence was measured from 28 days prior to first dose through 56 days after last dose, an average of 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Anthony, DO study director
Sumitomo Pharma America, Inc.
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Alvocidib (flavopiridol) and cytarabine (Ara-C) and Alvocidib (flavopiridol) in people with Acute Myeloid Leukemia (AML), run by Sumitomo Pharma America, Inc. at 18 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combined Complete Remission (time frame: Response assessments were measured from date of first dose through End of Treatment date, an average of 3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2023.