Recurrent Chronic Myelomonocytic LeukemiaPhase 1/2NCT04550442
Venetoclax and Azacitidine for the Treatment of Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
A Phase 1/2 study testing Azacitidine and Venetoclax in people with Recurrent Chronic Myelomonocytic Leukemia and Recurrent Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial investigates the side effects and best dose of venetoclax when given together with azacitidine and to see how well it works in treating patients with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Chronic Myelomonocytic Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Chronic Myelomonocytic Leukemia
- What is being tested?
- Azacitidine and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Sep 2020to 29 May 2026
- Phase
- Phase 1/2
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
- Participants with post HMA-failure high-risk MDS (Int-2 or high risk by the IPSS with overall score >/=1.5) with excess blasts >5% with failure defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy.
- Participants with relapsed/refractory chronic myelomonocytic leukemia (CMML) and therapy-related MDS are also eligible.
- Hydroxyurea is allowed to lower the white cell count </= 10,000/µl prior to initiation of venetoclax.
- Adequate hepatic function including total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and ALT/AST ≤ 3.0 x ULN unless considered due to leukemic involvement.
- Adequate renal function as calculated using the modified Cockcroft-Gault equation of ≥ 30ml/min, OR creatinine < 2x ULN, unless related to the disease.
- Signed written informed consent.
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- Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment.
- Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment.
- Age >/= 18 years of age.
- ECOG/PS ≤2
Who cannot join
- Participants having received any prior BCL2 inhibitor therapy.
- Participants with MDS with IPSS risk categories Low or Int-1 (overall IPSS score < 1.5).
- Participants with known HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at screening, only if required per local guidelines or institutional standards.
- Participants known to be positive for hepatitis B or C infection [HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on HBV-DNA PCR test for HBc Ab and/or HBs Ab positivity] with the exception of those with an undetectable viral load within 3 months of screening. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
- Participants has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
- Participants has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
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- Participants has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
- Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
- Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
- Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
- Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
- Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:
- Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
- Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.
- Participant has a white blood cell count > 10 × 109/L. (Hydroxyurea or leukapheresis are permitted to meet this criterion)
- Female subject has positive results for pregnancy test.
- Participants with (Grade > 1) unresolved from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I/II Study of Venetoclax in Combination With Azacitidine in Relapsed/Refractory High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
This phase I/II trial investigates the side effects and best dose of venetoclax when given together with azacitidine and to see how well it works in treating patients with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine together may help to control myelodysplastic syndrome or chronic myelomonocytic leukemia.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety and tolerability (phase 1) and overall response rate (ORR) (phase 2) of venetoclax in combination with azacitidine in patients with high risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with bone marrow excess blasts > 5% that are relapsed/refractory to prior hypomethylating agent (HMA) therapy.
SECONDARY OBJECTIVES:
- Rate of complete remission (CR). II. Rate of marrow/morphologic complete remission (mCR). III. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses).
IV. Rate of red blood cell (RBC) transfusion independence. V. Rate of platelet (PLT) transfusion independence. VI. Rate of cytogenetic response. VII. Rate of bone marrow blast response. VIII. Time to transformation to acute myeloid leukemia (AML). IX. Duration of response (DOR). X. Overall survival (OS). XI. Progression-free survival (PFS). XII. Time to next MDS treatment (TTNT). XIII. Event-free survival (EFS).
EXPLORATORY OBJECTIVE:
- To investigate the effects of therapy on MDS and to identify biological markers of response to venetoclax and/or its combination with azacitidine.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
Patients receive venetoclax orally (PO) daily on days 1-14 and azacitidine intravenously (IV) over 15 minutes or subcutaneously (SC) on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years.
- Conditions
- Recurrent Chronic Myelomonocytic Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Chronic Myelomonocytic Leukemia, Refractory Myelodysplastic Syndrome, Therapy-Related Myelodysplastic Syndrome
- Being tested
- Azacitidine, Venetoclax
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC
Given IV or SC
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (venetoclax, azacitidine) | Experimental | Patients receive venetoclax PO daily on days 1-14 and azacitidine IV over 15 minutes or SC on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: Azacitidine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) (Phase I)
The MTD is the highest dose level in which < 2 patients of 6 develop first cycle dose-limiting toxicity (DLT).
Measured: Up to 28 days
Overall response rate (ORR) (Phase II)
ORR is defined as the proportion of patients who had complete remission (CR), partial remission (PR) or marrow CR (mCR) lasting at least 4 weeks, or hematologic improvement (HI) lasting at least 8 weeks. Will estimate the overall response rate for the combination treatment, along with the 95% credible interval.
Measured: Up to 5 years post-treatment
Secondary outcomes (12)
Rate of CR
The association between CR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 5 years post-treatment
Rate of mCR
The association between mCR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 5 years post-treatment
Rate of hematologic improvement
Measured: Up to 5 years post-treatment
Rate of platelet transfusion independence
Measured: Up to 5 years post-treatment
Rate of red blood cell transfusion independence
Measured: Up to 5 years post-treatment
Rate of cytogenetic response
The correlation between cytogenetic response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 5 years post-treatment
Rate of bone marrow blast response
The correlation between bone marrow blast response and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 5 years post-treatment
Duration of response
Will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
Measured: The number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first, assessed up to 5 years post-treatment
Event-free survival
Will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
Measured: The number of days from the date of treatment initiation to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first, assessed up to 5 years post-treatment
Overall survival
Will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
Measured: The time from treatment start till death or last follow-up, assessed up to 5 years post-treatment
Progression free survival
Will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
Measured: The time from treatment to progression or last follow-up, assessed up to 5 years post-treatment
Time to transformation to acute myeloid leukemia (AML)
Will be estimated using the method of Kaplan and Meier. Comparisons by important subgroups will be made using the log-rank tests.
Measured: The time from treatment till transformation of AML or last follow-up, assessed up to 5 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start4 Sep 2020
- Primary completion29 May 2026
- Study completion29 May 2026
Why it stopped: \<75% participation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Chronic Myelomonocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04550442
- Sponsor's protocol ID
- 2020-0128
- Other IDs
- NCI-2020-06538, 2020-0128
- Status last verified
- Jan 2026
- First submitted
- 9 Sep 2020
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No