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AMLPhase 1NCT05287568

CC-486 and Venetoclax for Acute Myeloid Leukemia

A Phase 1 study testing Venetoclax and CC-486 in people with AML, run by University of Colorado, Denver at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is an open label, dose escalation Phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will… Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
AML
What is being tested?
Venetoclax and CC-486
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
2 sitesUnited States
Study dates
19 Dec 2022to Mar 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must have confirmation of non-APL AML by WHO criteria46 and have undergone at least one line of therapy (dose escalation and dose expansion R/R cohorts), or have had no prior lines of therapy (newly diagnosed cohort) Prior treatment with hydroxyurea or ATRA is allowed in the newly diagnosed cohort.
  • For the newly diagnosed cohort, subjects must be unlikely to tolerate standard intensive chemotherapy due to age, performance status, or comorbidities based on at least one of the following criteria:
  • age ≥75 years old OR b. age < 75 years old with at least one of the following: i. ECOG performance status of 3 ii. Cardiac history of CHF or documented EF ≤50% iii. pulmonary disease with DLCO ≤65% or FEV1 ≤65% iv. creatinine clearance ≥30 mL/min to < 45 mL/min based on the CKD-EPI Creatinine Equation (2021). https://www.kidney.org/content/ckd-epi-creatinine-equation-2021 v. any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy
  • Patients must have ECOG of 0 to 3 (if < 75 years old) or 0 to 2 (if ≥75 years old)
  • Transplant eligible patients can participate in the study and they are allowed to proceed with stem cell transplantation at any time during the study.
  • Subject must have a projected life expectancy of at least 12 weeks.
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  • Subject must have adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.
  • Subject must have adequate liver function as demonstrated by:
  • aspartate aminotransferase (AST) ≤ 3.0 × ULN*
  • alanine aminotransferase (ALT) ≤ 3.0 × ULN*
  • bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome* * Unless considered due to leukemic organ involvement
  • Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. Male subjects must agree to refrain from sperm donation from initial study drug administration until 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
  • Female subjects must be either:
  • Postmenopausal; defined as Age > 60 years with no menses for 12 or more months without an alternative medical cause; OR
  • Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR
  • If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose.
  • Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed screening or procedures.
  • Subject is informed that consumption of the following fruits is prohibited 3 days prior to the initiation of study treatment and throughout participation: grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit.

Who cannot join

  • Subject has known active CNS involvement from AML.
  • Subject is known to be positive for HIV. HIV testing is not required.
  • Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load. Hepatitis B or C testing is not required and subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag, anti-HBs+ and anti-HBc-) may participate.
  • Subject has any history of clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participating in this study including, but not limited to:
  • Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure > class 2, unstable angina, or myocardial infarction.
  • Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
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  • Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g. sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity.
  • Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment.
  • Subject has a history of other malignancies prior to study entry, with the exception of:
  • Adequately treated in situ carcinoma of the breast or cervix uteri
  • Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
  • Prostate cancer not requiring therapy beyond hormonal therapy
  • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
  • Subject has a white blood cell count > 25 × 109/L. Note: hydroxyurea or apheresis are permitted to meet this criterion.
  • Any subject who is a candidate for intensive induction therapy and agrees to receive this therapy.
  • Pregnant or breast-feeding females. A pregnancy test will be obtained at the time of screening.
  • Known or suspected hypersensitivity to azacitidine or mannitol.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites, 2 recruiting
  • CU Anschutz Medical Campus

    Aurora, Colorado, 80045

    Derek Schatz, derek.schatz@cuanschutz.edu

    Constance Brecl, 3035078221, constance.brecl@cuanschutz.edu

    Recruiting
  • University of Colorado Hospital

    Aurora, Colorado, 80045

    Derek Schatz, derek.schatz@cuanschutz.edu

    Constance Brecl, constance.brecl@cuanschutz.edu

    Recruiting

Other trials in United States

About this study

This is an open label, dose escalation Phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will commence, using venetoclax with the MTD of CC-486 in relapsed/refractory patients.

Read the detailed description

Subjects confirmed eligible will be admitted to the hospital for cycle 1, day 1. Venetoclax will be administered days 1-3, with the following schema:

100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter.

Subjects taking concomitant CYP3A4 inhibitors will be given the appropriate reduced doses of venetoclax.

Subjects will be monitored inpatient for tumor lysis syndrome (TLS) for at least 24 hours after administration of the venetoclax target dose. Venetoclax will continue at 400 mg daily until day 28, the completion of cycle 1.

During dose escalation, subjects will be accrued into two cohorts using two different doses of CC-486 (cohort 1=200 mg, cohort 2=300 mg, both to be administered orally on days 1-14 of a 28-day cycle).

Two bone marrow biopsies will be performed during the first cycle: day 4 or 5 (+2 days), and day 28. The day 28 bone marrow will be used for efficacy purposes. Subsequent cycles will have response assessment bone marrow biopsies day 28 of every cycle for subjects who have not responded (CR/CRi/MLFS); after a response occurs (CR/CRi/MLFS), subjects will have bone marrow biopsies on day 28 of every 3rd cycle until they have been on the study for one year, at which point they will have a bone marrow biopsy every 6 months until study discontinuation.

Once the MTD is established, or in the absence of an MTD, a recommendation for a CC-486 dose with venetoclax is made, the study will progress to the expansion phase. For the expansion phase, 10 subjects will be recruited. These will be patients with relapsed/refractory (R/R) disease who have never received venetoclax. On day 1 of cycle 1, subjects will receive CC-486 at the MTD or recommended CC-486 dose as determined from Phase I, and this will continue daily through day 14. Venetoclax will be dose escalated, as above, from 100 to 200 to 400 mg on days 1, 2 and 3, respectively, with inpatient monitoring for TLS, and with appropriate dose reduction if administered with a CYP3A4 inhibitor. Bone marrow biopsies will occur on day 4 or 5 (+2) and on day 28 of cycle 1. Subsequent response assessment bone marrow biopsies will occur on day 28 of every 3rd cycle for subjects who have achieved a response for 1 year from study entry and then every 6 months until study discontinuation, or on day 28 of every treatment cycle for subjects who do not achieve a response.

Conditions
AML
Being tested
Venetoclax, CC-486

What participants receive

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

  • VenetoclaxDrug

    Also called ABT-199, Abbvie

    Venetoclax is a potent, selective and orally bioavailable small molecule inhibitor of BCL-2 that binds with > 1,000-fold higher affinity to BCL-2 (Ki < 0.010 nM) than other apoptotic pathway proteins BCL-XL (Ki = 48 nm) or MCL-1 (Ki > 444 nM). Leukemia stem cells (LSCs) overexpress BCL-2, and BCL-2 overexpression has been associated with worse outcomes in AML.

  • CC-486Drug

    An oral formulation of azacitidine currently being developed for the treatment of hematological and solid malignancies.

Study groups in NCT05287568
Study groupRoleWhat they receive
Cohort 1 CC-486 200 mgExperimentalCC-486 200 mg will be administered orally on days 1-14 of a 28-day cycle. Venetoclax will be administered days 1-3, with the following schema: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter until day 28, the completion of cycle 1.
Receives: Drug: Venetoclax; Drug: CC-486
Cohort 2 CC-486 300 mgExperimentalCC-486 300 mg will be administered orally on days 1-14 of a 28-day cycle. Venetoclax will be administered days 1-3, with the following schema: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter until day 28, the completion of cycle 1.
Receives: Drug: Venetoclax; Drug: CC-486
Dose Expansion CohortExperimentalCC-486 MTD will be determine following the completion of Cohort 1 and Cohort 2 with venetoclax at 400 mg/day PI regimen for 28 days.
Receives: Drug: Venetoclax; Drug: CC-486

What is being measured

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

  1. Determine the maximum tolerated dose of CC-486 in combination with venetoclax

    Standard phase I 3+3 design. The first 3 subjects will be assigned to cohort 1. If none of the first three subjects' experiences DLT, escalation to cohort 2 is permitted. If one of the first three subjects' experiences DLT, a total of six subjects will be required in that dose cohort, and escalation will only be permitted if five of six subjects do not experience DLT. If more than one DLT is observed in the second cohort, this will be determined to be the maximally administered dose, and three more subjects will be enrolled in the first cohort if only three were previously treated at that dose. The MTD will be the cohort in which ≤1/6 subjects have dose limiting toxicity at the dose prior to the maximally administered dose. If the second cohort has ≤1/6 subjects with a DLT, the MTD will not have been reached, and the recommended dose for the expansion cohorts will be determined based on the safety, efficacy and pharmacodynamic outcomes from subjects treated in the first two cohorts.

    Measured: 7 years

Secondary outcomes (4)
  1. Adverse event profile of CC-486 in combination with venetoclax

    Subject safety will be assessed by reviewing AEs during planned and unplanned visits and physical and laboratory examinations from the time subject receives the first dose of study drug until safety follow up. AEs related to a procedure after consent will also be assessed. The investigator will assess and record AEs in detail including the date of onset, event diagnosis (if known) or sign/symptom, severity, time course (end date, ongoing, intermittent), relationship of the AE to the study drug, and any action taken. For SAEs considered unrelated to study drug, the investigator will provide another cause for the event. AEs may be recorded as the result of a response to a query, an observation by site personnel, or due to a report from a subject. All AEs will be followed to a satisfactory conclusion.

    Measured: 7 years

  2. Response Rate

    Response rate, with responses defined as complete remission (CR), CR with incomplete blood count recovery (CRi) and morphologic leukemia free state (MLFS) for newly diagnosed and relapsed and refractory patients

    Measured: 5 - 7 years

  3. Time to Response

    Time to response for newly diagnosed and relapsed and refractory patients

    Measured: 5-7 Years

  4. Response Duration

    Response duration for newly diagnosed and relapsed and refractory patients

    Measured: 5-7 years

Timeline

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

  1. First posted18 Mar 2022
  2. Study start19 Dec 2022
  3. Primary completion23 Mar 2027 (estimated)
  4. Study completionMar 2029 (estimated)

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
This is an open label, dose escalation phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will commence, using venetoclax with the MTD of CC-486 in relapsed/refractory patients.
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05287568
Sponsor's protocol ID
20-1319.cc
Status last verified
Jan 2026
First submitted
9 Mar 2022
Last updated
15 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: At this time, there is no plan to share individual patient data.

Publications

  • Amaya ML, Abbott D, McMahon CM, Schwartz MS, Gutman JA, Kent A, Angelos MG, Sohalski C, Belachew A, Dell-Martin J, Anttila K, Stevens BM, D'Alessandro A, Showers WM, Gillen AE, Jordan CT, Pollyea DA. A Phase 1/1b Study of the All-Oral Regimen CC-486 and Venetoclax in Acute Myeloid Leukemia. Blood Adv. 2026 Jul 24:bloodadvances.2026020179. doi: 10.1182/bloodadvances.2026020179. Online ahead of print.

    PubMed 42498285

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax and CC-486 in people with AML, run by University of Colorado, Denver at 2 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 18 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Derek Schatz (7208480628, derek.schatz@cuanschutz.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the maximum tolerated dose of CC-486 in combination with venetoclax (time frame: 7 years). 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 NCT05287568, which also lists 1 linked publication.

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 15 Jan 2026.

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