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Chronic Myelomonocytic LeukemiaPhase 1/2NCT06085638

Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia

A Phase 1/2 study testing Azacitidine, Tamibarotene and Venetoclax in people with Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

To learn if adding venetoclax to the chemotherapy combination of tamibarotene and azacitidine is more effective than tamibarotene and azacitidine alone in treating higher-risk CMM Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Chronic Myelomonocytic Leukemia
What is being tested?
Azacitidine, Tamibarotene 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
No sites listed yet
Study dates
14 Sep 2023to 20 Oct 2023
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

  • Patients must be at least 18 years old
  • CMML according to WHO and:
  • Cohort 1: HMA-naïve CMML-2 or HMA-naïve CMML-1, with Int-1, Int-2 or high risk by the Molecular CMML-Specific Prognostic Scoring system (CPSS-Mol) in whom HMA therapy is indicated.
  • Cohorts 2 and 3: CMML-1 or CMML-2 and failure to HMA defined as no response after 4 cycles of azacitidine, decitabine, guadecitabine, oral decitabine/cedazuridine, ASTX030, or relapse or progression after any number cycles.
  • ECOG Performance Status of ≤2.
  • Patients must have the following laboratory values:
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  • total bilirubin ≤1.5 × the ULN (Patients with Gilbert's syndrome can be included with total bilirubin >1.5 x ULN as long as direct bilirubin is < 35% of total bilirubin and ≤ 1.5 x ULN) ALT and AST ≤2.5 × ULN, and creatinine clearance ≥60 mL/min based on the Cockcroft-Gault Glomerular Filtration Rate estimation.
  • Patients must have a serum or high-sensitivity urine pregnancy test (for females of childbearing potential) that is negative at the Screening Visit and within 72 hrs prior to initiation of treatment (first dose of study drug).
  • Patients must be willing and able to comply with the scheduled study visits, treatment plans, laboratory tests, use of 2 methods of birth control (including a barrier method) for patients who are women of childbearing potential (WOCBP) and for male patients
  • White blood cell (WBC) count <50,000/L (<10,000/L prior to starting Cycle 1 Day 1 with venetoclax on Cohorts 2 and 3). Hydroxyurea may be used to control leukocytosis prior to and for the first 28 days of study treatment (i.e cycle 1). Use of hydroxyurea beyond this point may be permitted as clinically indicated, on a case-by-case basis and after discussion with the PI.

Who cannot join

  • Patients who are currently receiving treatment for a malignancy (not including basal cell carcinoma, non melanoma skin cancer, cervical carcinoma in situ, or localized prostate cancer treated with hormone therapy). Patients with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit.
  • Patients who have an active, life-threatening, or clinically-significant uncontrolled systemic infection requiring hospitalization.
  • Patients who have a known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy).
  • Immunocompromised patients with increased risk of opportunistic infections, including known HIV-positive patients with CD4 counts ≤350 cells/mm3 or history of opportunistic infection in the last 12 months. Note: To ensure that effective ART, when used in eligible HIV-positive patients, is tolerated and that toxicities are not confused with investigational drug toxicities, patients should be on an established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to the Screening Visit.
  • Patients with a known active or chronic hepatitis B or active HCV infection. Patients with a history of HCV infection who have completed curative therapy for HCV at least 12 weeks before the Screening Visit and have a documented undetectable viral load at the Screening Visit are eligible for enrollment.
  • Patients who have other severe acute or chronic medical conditions (and/or psychiatric conditions or laboratory abnormalities) that may increase the expected risk to the patient (i.e., the risk associated with the study participation or study drug administration) or that may interfere with the interpretation of study results or, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
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  • Patients who have not adequately recovered from a major surgery within 4 weeks prior to starting study drug administration.
  • Patients with a diagnosis of hypervitaminosis A or patients taking vitamin A supplements >10,000 IU/day, unless treatment is discontinued at least 7 days prior to the first dose of the study drug.
  • Patients received strong inducers of CYP3A4 (see Appendix 4) within 2 weeks prior to the first tamibarotene administration.
  • Patients who received any other investigational agents within 4 weeks prior to the Screening Visit or <5 half-lives since completion of previous investigational therapy have elapsed, whichever is shorter.
  • Patients require concurrent treatment with any investigational or approved oncology agent.
  • Patients with Grade ≥2 hypertriglyceridemia, defined as >300 mg/dL (CTCAE, version 5).
  • Patients with QTc interval >480 msec based on average of triplicate ECG readings at the Screening Visit using the Fridericia formula (QTcF), with the exception of patients with right bundle branch block or left bundle branch block.
  • Pregnant females, breastfeeding females, and males or females of childbearing potential not willing to comply with contraceptive requirements (as described in Appendix 2)
  • Patients who have a hypersensitivity to tamibarotene, azacitidine or venetoclax, or to any of their excipients, including sodium hydrosulfite.
  • Patients for whom treatment with tamibarotene is contraindicated.

About this study

To learn if adding venetoclax to the chemotherapy combination of tamibarotene and azacitidine is more effective than tamibarotene and azacitidine alone in treating higher-risk CMM

Read the detailed description

Primary Objectives:

  • Cohort 1: Characterize the safety and toleratbility of the combination of azacitidine and tamibarotene in newly diagnosed CMML.
  • Cohort 2 and 3: Characterize the safety and tolerability of tamibarotene in combination with azacitidine and venetoclax in relapsed higher risk CMML.

Secondary Objectives:

  • Cohort 1: Characterize the preliminary clinical activity of tamibarotene in combination with azacitidine defined by complete response (CR) rate, following MDS/MPN IWG response criteria (Appendix 1),
  • Cohort 2: Characterize the safety and tolerability of tamibarotene in combination with azacitidine and venetoclax in relapsed higher risk CMML.
  • Cohort 3: Characterize the clinical activity of tamibarotene in combination with azacitidine and venetoclax by overall response rate (ORR) in relapsed higher risk CMML.
  • To characterize additional clinical activity outcomes such as duration of response, leukemia-free survival (LFS), event-free survival (EFS) and overall survival (OS).
  • To evaluate differences in response and efficacy outcomes by MDS/MPN IWG response criteria based on RARA expression levels and positivity.
  • To correlate response with disease subtype and genomic profile
  • To evaluate changes in clonal composition and VAF of identified mutations with therapy.
Being tested
Azacitidine, Tamibarotene, Venetoclax
Medical subject headings
Leukemia, Myelomonocytic, Chronic

What participants receive

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

  • AzacitidineDrug

    Also called 5-azacytidine, 5-aza, Vidaza™, 5-AZC

    Given by SC (under the skin) or IV (vein)

  • TamibaroteneDrug

    Given by PO

  • VenetoclaxDrug

    Also called ABT-199, GDC-0199

    Given by PO

    TAMIBAROTENE Azacitidine Azacitidine, 5-azacytidine, 5-aza, Vidaza™, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine Venetoclax ABT-199, GDC-0199, Venetoclax

Study groups in NCT06085638
Study groupRoleWhat they receive
Arm1: Cohort 1: Azacitidine + TamibaroteneExperimentalParticipants will receive azacitidine on Days 1-7 of each cycle and tamibarotene 2 times a day every day. Up to 20 participants will be enrolled in Cohort 1.
Receives: Drug: Azacitidine; Drug: Tamibarotene
Arm2: Cohort 2,3: Azacitidine + Tamibarotene + VenetoclaxExperimentalParticipants will receive azacitidine on Days 1-7 of each cycle, tamibarotene 2 times a day every day, and venetoclax on either Days 1-7 or Days 1-14 of each cycle, depending on the dose level you are assigned at enrollment. Up to 12 participants will be enrolled in Cohort 2. Once Cohort 2 is complete, Cohort 3 will begin. Participants in Cohort 3 will receive the recommended dosing schedule found in Cohort 2 (azacitidine on Days 1-7, tamibarotene 2 times a day every day, and venetoclax on either Days 1-7 or Days 1-14
Receives: Drug: Azacitidine; Drug: Tamibarotene; Drug: Venetoclax

What is being measured

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

  1. Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Measured: through study completion; an average of 1 year

Timeline

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

  1. First posted17 Oct 2023
  2. Study start14 Sep 2023
  3. Primary completion20 Oct 2023
  4. Study completion20 Oct 2023

Why it stopped: Zero participants accrued

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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06085638
Sponsor's protocol ID
2023-0110
Other IDs
NCI-2023-08582
Status last verified
Mar 2024
First submitted
10 Oct 2023
Last updated
7 Mar 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Azacitidine, Tamibarotene and Venetoclax in people with Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center.

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 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 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

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?

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year). 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 NCT06085638.

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 7 Mar 2024.

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