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Recurrent Acute Myeloid LeukemiaPhase 1/2NCT04493099

Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML

A Phase 1/2 study testing Alvocidib Hydrochloride, Decitabine and Venetoclax in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial investigates the side effects and best dose of alvocidib when given together with decitabine and venetoclax and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed), has not responded to previous treatment (refractory), or as frontline treatment… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alvocidib Hydrochloride, Decitabine and Venetoclax
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Oct 2020to 12 Oct 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Diagnosis of relapsed or refractory acute myeloid leukemia by World Health Organization (WHO) criteria. Unfit/frail patients with newly diagnosed AML are also eligible if not considered good candidates to receive a higher intensity therapy
  • A patient is considered unfit or frail if has three or more of the five factor below:
  • Unintentional weight loss of 10 pounds or more in a year
  • General feeling of exhaustion
  • Weakness as measured by grip strength
  • Slow walking speed
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  • Low levels of physical activity
  • Eastern Cooperative Oncology Group (ECOG) performance status score of =< 3
  • Total serum bilirubin =< 2 x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to =< 3 x ULN
  • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) =< 3 x ULN; or =< 5 x ULN in case of suspected leukemic liver involvement
  • Serum creatinine =< 2.0 mg/dl
  • Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (B-HCG) pregnancy test result within 1 week (+/-3 days) prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug. Effective methods of birth control include:
  • Birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin)
  • Intrauterine devices (IUDs)
  • Condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide
  • Abstinence
  • Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation, oophorectomy, and/or hysterectomy
  • Males who have partners of childbearing potential must agree to use an effective contraceptive method (such as condom used with spermicide or abstinence) during the study and for 30 days following the last dose of study drug
  • Patients or their legally authorized representative must provide written informed consent

Who cannot join

  • Patients with t(15;17) karyotype abnormality or acute promyelocytic leukemia
  • History of another primary invasive malignancy that has not been definitively treated and in remission. Patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses)
  • Presence of clinically significant uncontrolled central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
  • Evidence of active cerebral/meningeal disease. Patients may have history of CNS leukemic involvement if definitively treated with prior therapy and no evidence of active disease at the time of consent with at least 2 consecutive spinal fluid negative assessments for residual leukemia and negative imaging (imaging required only if previously showing evidence of CNS leukemia not otherwise documented by spinal fluid assessment)
  • Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV. Patients with a cardiac ejection fraction (as measured by either multigated acquisition scan [MUGA] or echocardiogram) < 45% are excluded
  • Patients with uncontrolled, active infections (viral, bacterial, or fungal)
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  • Known active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV)
  • Patients with liver cirrhosis or other serious active liver disease or with suspected active alcohol abuse
  • Allogeneic hematopoietic cell transplantation (HSCT) within 6 months before the start of protocol-specified therapy, or with active acute/chronic graft-versus-host disease (GvHD) requiring systemic treatment; or receiving immunosuppression for GvHD prophylaxis within 2 weeks from the start of study therapy
  • Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exception:
  • To reduce tumor burden, leukocytosis (circulating blast count) or palliation: Intravenous cytarabine and/or hydroxyurea. No washout is necessary for these agents. Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment
  • Females who are pregnant or lactating
  • Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with institution's standards
  • Other severe, uncontrolled acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study
  • Prior treatment with alvocidib
  • Prior use of venetoclax single agent or any venetoclax-based combination therapy is allowed

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase 1/2 Study of Alvocidib in Combination With Decitabine and Venetoclax in Patients With Relapsed or Refractory AML or as Frontline Therapy in Unfit Patients With AML

This phase I/II trial investigates the side effects and best dose of alvocidib when given together with decitabine and venetoclax and to see how well it works in treating patients with acute myeloid leukemia that has come back (relapsed), has not responded to previous treatment (refractory), or as frontline treatment for patients unable to receive other therapies (unfit). Alvocidib, decitabine, and venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety of alvocidib hydrochloride (alvocidib) in combination with decitabine and venetoclax in relapsed or refractory patients with acute myeloid leukemia (AML) or as frontline therapy in unfit/frail patients with AML. (Phase I) II. To determine the efficacy alvocidib in combination with decitabine and venetoclax in relapsed or refractory patients with acute myeloid leukemia (AML) or as frontline therapy in unfit/frail patients with AML. (Phase II)

SECONDARY OBJECTIVE:

  1. To determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables, including overall survival (OS), event-free survival (EFS) and duration of response (DOR) of patients treated with this combination.

EXPLORATORY OBJECTIVES:

  1. To determine the minimal residual disease (MRD) after treatment with this combination and its impact in long-term outcome.

II. To determine the effect of the level of pre-treatment expression of BCL-2 and MCL-1 (by BH3 profiling) with response to this combination.

III. To determine the effect of this treatment combination on responding patients transitioning to hematopoietic stem cell transplantation (HSCT).

OUTLINE: This is a phase I, dose-escalation study of alvocidib followed by a phase II study.

INDUCTION: Patients receive decitabine intravenously (IV) over 1 hour on days 1-10, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10, or 1-14, and venetoclax orally (PO) once daily (QD) on days 1-14 in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients receive decitabine IV over 1 hour on days 1-5, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10 or 1-14, and venetoclax PO QD on days 1-10. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks.

Being tested
Alvocidib Hydrochloride, Decitabine, Venetoclax
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alvocidib HydrochlorideDrug

    Also called 4H-1-Benzopyran-4-one, 2-(2-chlorophenyl)-5, 7-dihydroxy-8-(3-hydroxy-1-methyl-4-piperidinyl)-, hydrochloride, (-)-cis-, Flavopiridol Hydrochloride, HL-275, HMR 1275

    Given IV

  • DecitabineDrug

    Also called 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine

    Given IV

  • VenetoclaxDrug

    Also called ABT-0199, ABT-199, ABT199, GDC-0199

    Given PO

Study groups in NCT04493099
Study groupRoleWhat they receive
Treatment (decitabine, alvocidib hydrochloride, venetoclax)ExperimentalINDUCTION: Patients receive decitabine IV over 1 hour on days 1-10, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10, or 1-14, and venetoclax PO QD on days 1-14 in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive decitabine IV over 1 hour on days 1-5, alvocidib hydrochloride IV over 1 hour on days 1-3, 1-5, 1-7, 1-10 or 1-14, and venetoclax PO QD on days 1-10. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Alvocidib Hydrochloride; Drug: Decitabine; Drug: Venetoclax

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall incidence and severity of all adverse events (Phase I)

    Measured using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: Up to 6 years

  2. Overall response rate (ORR) (Phase II)

    Will estimate the response rate for the combination treatment, along with the 95% credible interval.

    Measured: Up to 6 years

Secondary outcomes (3)

  1. Duration of response

    The duration of response is defined as the number of days from the date of initial response (partial response [PR] or better) to the date of first documented disease progression/relapse or death, whichever occurs first.

    Measured: Up to 6 years

  2. Event free survival

    Event-free survival is defined as the number of days from the date of treatment initiation (e.g., cycle 1 day 1 [C1D1]) to the date of documented treatment failure, relapses from complete response (CR), or death from any cause, whichever occurs first, and will be calculated for all patients. Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

    Measured: Up to 6 years

  3. Overall survival

    Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.

    Measured: From treatment start till death or last follow-up, assessed up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2020
  2. Study startOct 2020 (estimated)
  3. Primary completion12 Oct 2020
  4. Study completion12 Oct 2020

Why it stopped: The original sponsor was acquired by a new company and has elected to end funding for all Investigator Sponsored Trials (ISTs)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04493099
Sponsor's protocol ID
2019-1053
Other IDs
NCI-2020-05266, 2019-1053
Status last verified
Nov 2020
First submitted
27 Jul 2020
Last updated
12 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alvocidib Hydrochloride, Decitabine and Venetoclax in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 19 inclusion and 16 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: withdrawn, as of the sponsor's last update on 12 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Overall incidence and severity of all adverse events (Phase I) (time frame: Up to 6 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04493099.

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 12 Nov 2020.

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