Myelodysplastic SyndromesPhase 2NCT05365035
A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
A Phase 2 study testing Cladribine, Cytarabine and Venetoclax in people with Myelodysplastic Syndromes and Myeloproliferative Chronic Myelomonocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomonocytic leukemia (CMML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Myeloproliferative Chronic Myelomonocytic Leukemia
- What is being tested?
- Cladribine, Cytarabine and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Sep 2022to 31 Dec 2027
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >/= 18 years.
- Diagnosis of MDS or CMML by WHO and:
- MDS relapsed cohort (Cohort A): MDS with IPSS-R score >3.5 and >5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- CMML relapsed cohort (Cohort B): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS HMA-naïve cohort (Cohort C): MDS with IPSS-R score >3.5 and >/= 10% blasts
- CMML HMA-naïve cohort (Cohort D): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of >5cm below costal margin or by sonographic volumetric assessment, platelets <100x109/L, Hgb level <10g/dL, WBC >13x109/L, clonal cytogenetic abnormality (other than monosomy Y) or high risk mutations (ASXL1, RUNX1, SETBP1, BRAF, NRAS, KRAS, PTPN11, NF1, CBL).
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- MDS/MPN relapsed cohort (Cohort E): MDS/MPN-NOS, MDS/MPN with neutrophilia (atypical CML) or MDS/MPN-RS-T with >5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS/MPN HMA-naïve cohort (Cohort F): MDS/MPN-NOS or MDS/MPN with neutrophilia (atypical CML) with
- >/=10% blasts or
- with >5% blasts at least one of the following high-risk features: splenomegaly >5cm below costal margin, WBC >13x109/L, high risk cytogenetic or molecular features (ASXL1, SETBP1, i(17q), TP53) or
- who might not be deemed to benefit from HMA therapy due to proliferative or extramedullary disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- Creatinine clearance > 30 ml/min no end/stage renal disease (using Cockcroft-Gault)
- Adequate hepatic function with total bilirubin 2x ULN, AST or ALT 2.5 xULN unless deemed to be due to underlying disease involvement.
- Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
- Patient must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
- English and Non-English speaking patients will be allowed
Who cannot join
- Uncontrolled infection not adequately responding to appropriate antibiotics
- New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50% by echocardiogram or multigated acquisition (MUGA) scan.
- History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.
- Female patients who are pregnant or lactating.
- Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermidical jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
- Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
- Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Guillermo Bravo, MD, 713-794-3604, gmontalban1@mdanderson.org
Guillermo Bravo, MD
About this study
To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomonocytic leukemia (CMML).
Read the detailed description
Primary Objectives:
- To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk MDS with excess blasts and higher-risk CMML.
- MDS relapsed cohort (Cohort A, N=20): MDS with Int-2 or High risk IPSS and >5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- CMML relapsed cohort (Cohort B, N=10): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS HMA-naïve cohort (Cohort C, N=20): MDS with Int-2 or High risk by IPSS and >10% blasts OR diagnosis
- CMML HMA-naïve cohort (Cohort D, N=10): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of >5cm below costal margin, platelets <100x109/L, Hgb level <10g/dL, WBC >13x109/L, clonal cytogenetic abnormality (other than monosomy Y).
Secondary Objectives:
- To evaluate responses by 2015 IWG MDS/MPN response criteria in patients with MDS/MPN and by 2023 IWG response criteria in all patients (Appendix).
- To assess overall survival (OS), duration of response, leukemia-free survival (LFS), and relapse-free survival (RFS).
- To evaluate proportion of transplant-candidate patients bridged to allogeneic stem-cell transplant.
- Correlative studies including correlation of response with disease subtype and genomic profile.
- To evaluate changes in clonal composition and VAF of identified mutations with therapy.
- Being tested
- Cladribine, Cytarabine, Venetoclax, Azacitidine
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called Leustatin®, 2-CdA
Given by Vein (IV)
CytarabineDrug
Also called Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochloride
Given under the skin; subcutaneous injection (SQ)
VenetoclaxDrug
Also called ABT-199, GDC-0199
Given by PO
AzacitidineDrug
Also called 5-azacytidine, 5-aza, Vidaza™, 5-AZC
Given by IV or subcutaneous injection (SQ)
| Study group | Role | What they receive |
|---|---|---|
| cladribine, cytarabine, venetoclax, and azacitidine | Experimental | Participants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18 Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Venetoclax; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the overall survival (OS).
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.
- First posted6 May 2022
- Study start23 Sep 2022
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillermo Bravo, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05365035
- Sponsor's protocol ID
- 2021-1116
- Other IDs
- NCI-2022-03803
- Status last verified
- Jun 2026
- First submitted
- 26 Apr 2022
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
- ClinicalTrials.gov ID
- NCT05365035
- Acronym / sponsor ID
- 2021-1116
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 23 Sep 2022 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 6 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if the combination of cladribine, cytarabine, venetoclax, and azacitidine can help to control higher-risk myelodysplastic syndrome (MDS) with excess blasts and/or higher-risk chronic myelomonocytic leukemia (CMML).
Detailed description
Primary Objectives:
- To determine the efficacy, safety and tolerability of the combination of cladribine, cytarabine and venetoclax in higher-risk MDS with excess blasts and higher-risk CMML.
- MDS relapsed cohort (Cohort A, N=20): MDS with Int-2 or High risk IPSS and >5% blasts with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- CMML relapsed cohort (Cohort B, N=10): CMML 1 or 2 with no response after 6 cycles of azacitidine, decitabine, guadecitabine, CC-486 or ASTX727 (decitabine/cedazuridine) or relapse or progression after any number of cycles
- MDS HMA-naïve cohort (Cohort C, N=20): MDS with Int-2 or High risk by IPSS and >10% blasts OR diagnosis
- CMML HMA-naïve cohort (Cohort D, N=10): CMML-2; OR CMML-1 with at least one of the following high-risk features: extramedullary disease, splenomegaly of >5cm below costal margin, platelets <100x109/L, Hgb level <10g/dL, WBC >13x109/L, clonal cytogenetic abnormality (other than monosomy Y).
Secondary Objectives:
- To evaluate responses by 2015 IWG MDS/MPN response criteria in patients with MDS/MPN and by 2023 IWG response criteria in all patients (Appendix).
- To assess overall survival (OS), duration of response, leukemia-free survival (LFS), and relapse-free survival (RFS).
- To evaluate proportion of transplant-candidate patients bridged to allogeneic stem-cell transplant.
- Correlative studies including correlation of response with disease subtype and genomic profile.
- To evaluate changes in clonal composition and VAF of identified mutations with therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cladribine, cytarabine, venetoclax, and azacitidine | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: Venetoclax, Drug: AzacitidineParticipants will receive cladribine, cytarabine, and venetoclax for 2 cycles and then azacitidine and venetoclax for 2 cycles. Participants will repeat this pattern of 2 cycles each for up to a total of 18 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age >/= 18 years.
- Diagnosis of MDS or CMML by WHO and:
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
- Creatinine clearance > 30 ml/min no end/stage renal disease (using Cockcroft-Gault)
- Adequate hepatic function with total bilirubin 2x ULN, AST or ALT 2.5 xULN unless deemed to be due to underlying disease involvement.
Key exclusion criteria (7 listed)
- Uncontrolled infection not adequately responding to appropriate antibiotics
- New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF <50% by echocardiogram or multigated acquisition (MUGA) scan.
- History of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias.
- Female patients who are pregnant or lactating.
- Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermidical jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
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 |
|---|---|---|
| CladribineAlso: Leustatin®, 2-CdAGiven by Vein (IV) | Drug | cladribine, cytarabine, venetoclax, and azacitidine |
| CytarabineAlso: Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochlorideGiven under the skin; subcutaneous injection (SQ) | Drug | cladribine, cytarabine, venetoclax, and azacitidine |
| VenetoclaxAlso: ABT-199, GDC-0199Given by PO | Drug | cladribine, cytarabine, venetoclax, and azacitidine |
| AzacitidineAlso: 5-azacytidine, 5-aza, Vidaza™, 5-AZCGiven by IV or subcutaneous injection (SQ) | Drug | cladribine, cytarabine, venetoclax, and azacitidine |
Primary outcome
To establish the overall survival (OS).
Time frame: through study completion, an average of 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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.
Guillermo Bravo, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cladribine, Cytarabine and Venetoclax in people with Myelodysplastic Syndromes and Myeloproliferative Chronic Myelomonocytic 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 17 inclusion and 7 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 5 Jun 2026. 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 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?
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 Guillermo Bravo, MD ((713) 794-3604, gmontalban1@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To establish the overall survival (OS). (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?
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 5 Jun 2026.