Acute Myeloid Leukemia (AML)Phase 1NCT07780565
Study of Monzosertib In Patients With R/R AML Or High-Risk Myelodysplastic Syndrome
A Phase 1 study testing Monzosertib, Posaconazole and Isavuconazole in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to find the recommended dose of monzosertib in patients with relapsed/refractory AML and high-risk MDS. The safety and effects of monzosertib will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome
- What is being tested?
- Monzosertib, Posaconazole and Isavuconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2027to 30 Aug 2031
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients need to be adults ≥18 years with R/R AML, 'MDS/AML', MDS, or CMML, per the ICC 2022 or the WHO 2022 with ≥5% blasts at screening. 6,7
- Relapsed or refractory disease is defined as: patient having received and have progressed or relapsed or intolerant to standard regimens, e.g., as listed in NCCN guidelines, or declined treatment with such therapies.
- This may include at least one cycle of intensive chemotherapy for AML, or for AML/MDS/CMML at least 2 cycles of BCL2 inhibitor based lower intensity regimen or 4 cycles of HMA-based regimens without BCL2 inhibitor, or clear progression during such treatment.
- "Treated secondary AML" i.e., patients with antecedent hematological disorder, e.g., MDS, CMML, MPD/MPN, who progress to AML despite receiving treatment adequate for AML (per NCCN) for the antecedent hematological disorder, will be eligible due to recognized poor outcomes similar to R/R AML.
- 8,9
- Patients with actionable mutations with available FDA-approved therapies, e.g., FLT3, IDH1/2, menin inhibitors may be enrolled after they have exhausted or ineligible for appropriate lines of FDA approved treatment options.
Show all 14Show fewer
- ECOG PS 0 to 2
- Adequate hepatic function (total bilirubin ≤ 1.5 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT ≤ 2.5 x ULN unless considered due to leukemic involvement, in which case total bilirubin or AST and/or ALT ≤ 3 x ULN will be considered eligible).
- Adequate renal function with creatinine clearance ≥ 30 mL/min calculated by the CockcroftGault formula or MDRD equation.
- Patients relapsing after allo-SCT may be eligible if they have recovered from all transplantrelated toxicities and are off all immunosuppression, with no more than grade 1 chronic GVHD. Physiologic ("replacement") dose of steroids (≤10 mg prednisone or equivalent) may be acceptable. Patients must be off all immunosuppression, including calcineurin inhibitors, for at least 2 weeks or 5 half-lives, whichever is longer, prior to enrollment on study.
- The effects of these agents on the developing human fetus are unknown. For this reason, and because other therapeutic agents used in this trial may be teratogenic, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for at least 90 days after last treatment.
- This includes all female patients between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: i. Postmenopausal (no menses in greater than or equal to 12 consecutive months). ii. History of hysterectomy or bilateral salpingo-oophorectomy. iii. Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range, who have received whole pelvic radiation therapy). iv. History of bilateral tubal ligation or another surgical sterilization procedure.
- Approved methods of birth control are as follows: Hormonal contraception (i.e., birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), tubal ligation or hysterectomy, subject/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patient has a white blood cell count > 15 x 10⁹/L. Hydroxyurea, and/or cytarabine use as supportive care is permitted to meet this criterion.10
- Prior use of any cytotoxic chemotherapy, targeted therapy, immunotherapy, or investigational therapies within 2 weeks or 5 half-lives (whichever is shorter), prior to first dose of study treatment. Patients should have recovered from all prior therapy related toxicities. Patients may receive hydroxyurea or cytarabine for control of WBC count during this washout period.
- Patient has uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment.
- Decompensated congestive heart failure, clinically significant, uncontrolled arrhythmia prolonged QT interval corrected for heart rate (QTcF) to greater than 450 msec, or long QT syndrome, or history of Torsades de pointes. Patients with bundle branch block or pacemaker and prolonged QTc interval are permitted after appropriate correction, (e.g., Bogossian formula, or others) or after discussion with the PI and/or cardiologist. Acute respiratory failure, unstable or decompensated pulmonary disease
- Patients with any severe gastrointestinal or metabolic condition or gastric bypass, which could interfere with absorption of oral drug.
- Active hepatitis B (HBV) or Hepatitis C (HCV) infection with detectable viral DNA or RNA, respectively, or known HIV infection. Patients with history of hepatitis with undetectable viral load will be eligible.
Show all 12Show fewer
- Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator.
- Any previous malignancy, except when the patient has completed definitive curative-intent treatment with chemotherapy and/or surgery and/or radiotherapy at least 1 month prior to enrollment. Patients having completed definitive treatment for the following conditions may be eligible immediately after completion of definitive curative-intent therapy, after healing of wounds, and no evidence of residual disease by examination or imaging or cytology/pathology, e.g., non-melanoma skin cancers, or any carcinoma in-situ, e.g., ductal carcinoma in situ, urothelial cancer, cervical cancer, localized prostate cancer, pre-cancerous colon polyp, etc.
- Major surgery within 4 weeks prior to screening or a major wound that has not fully healed.
- Patients under legal protection measure (guardianship, trusteeship or safeguard of justice) and/or uncontrolled psychiatric comorbidities, ongoing illicit substance abuse, inability, any impairment or unwillingness to comply with the treatments, follow-up, requirements and procedures of this clinical trial.
- Nursing women, women of childbearing potential (WOCBP) with positive urine or serum pregnancy test, or WOCBP who are not willing to maintain adequate contraception.
- Pregnant women are excluded from this study because study agents may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with study agents, breastfeeding should be discontinued if the mother is treated on this study.
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
UT MD Anderson Cancer Center
Houston, Texas, 77030
Abhishek Maiti, MBBS, 713-745-3228, amaiti@mdanderson.org
Abhishek Maiti, MBBS
About this study
Official title: Phase 1b Study of Monzosertib In Patients With Relapsed Or Refractory Acute Myeloid Leukemia Or High-Risk Myelodysplastic Syndrome
The goal of this clinical research study is to find the recommended dose of monzosertib in patients with relapsed/refractory AML and high-risk MDS. The safety and effects of monzosertib will also be studied.
Read the detailed description
Primary Objective:
To study the safety and tolerability of monzosertib in terms of treatment emergent adverse events (TEAE) and dose limiting toxicities (DLT).
To establish the RP2D of monzosertib based on the totality of the data.
Secondary Objectives:
- To estimate rate of CR/CRh by 4 cycles of treatment
- To estimate overall response rate (ORR) by 4 cycles of treatment. ORR will be defined as CR/CRh/CRi/MLFS/PR for AML and MDS/AML, and CR/CR equivalent/PR/CRL/CRh/HI for MDS or CMML
- To determine duration of response (DOR) of CR/CRh
- To determine overall survival (OS)
Exploratory Objective:
- To characterize the pharmacokinetics (PK) and drug-drug interactions with azole antifungals.
- To characterize pharmacodynamic (PD) biomarkers with monzosertib treatment
- To explore biomarkers of response and resistance
- Being tested
- Monzosertib, Posaconazole, Isavuconazole
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MonzosertibDrug
Give by mouth
PosaconazoleDrug
Also called Noxafil
Given by mouth
IsavuconazoleDrug
Also called Cresemba, Isavuconazonium sulfate
Given by mouth
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Phase 1b ESC Arm 1 Treatment - Monzosertib with No Azoles | Experimental | Participants may initiate treatment in the inpatient environment, at the discretion of the treating physician. Receives: Drug: Monzosertib |
| Arm 2: Phase 1b ESC Arm 2 Treatment - Monzosertib with Posaconazole | Experimental | Participants may initiate treatment in the inpatient environment, at the discretion of the treating physician. Receives: Drug: Monzosertib; Drug: Posaconazole |
| Arm 3: Phase 1b ESC Arm 3 Treatment - Monzosertib with Isavuconazole | Experimental | Participants may initiate treatment in the inpatient environment, at the discretion of the treating physician. Receives: Drug: Monzosertib; Drug: Isavuconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse Events (AEs).
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.
- First posted21 Aug 2026
- Study start1 Jan 2027 (estimated)
- Primary completion30 Aug 2029 (estimated)
- Study completion30 Aug 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Carna Biosciences, Inc.
- Responsible party
- Sponsor
- Investigators
- Abhishek Maiti, MBBS, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07780565
- Sponsor's protocol ID
- 2026-0198
- Other IDs
- NCI-2026-06050
- Status last verified
- Aug 2026
- First submitted
- 17 Aug 2026
- Last updated
- 21 Aug 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 21 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b Study of Monzosertib In Patients With Relapsed Or Refractory Acute Myeloid Leukemia Or High-Risk Myelodysplastic Syndrome
- ClinicalTrials.gov ID
- NCT07780565
- Acronym / sponsor ID
- 2026-0198
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Carna Biosciences, Inc.
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 30 Aug 2029 (estimated)
- Study completion
- 30 Aug 2031 (estimated)
- First posted
- 21 Aug 2026 (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.
The goal of this clinical research study is to find the recommended dose of monzosertib in patients with relapsed/refractory AML and high-risk MDS. The safety and effects of monzosertib will also be studied.
Detailed description
Primary Objective:
To study the safety and tolerability of monzosertib in terms of treatment emergent adverse events (TEAE) and dose limiting toxicities (DLT).
To establish the RP2D of monzosertib based on the totality of the data.
Secondary Objectives:
- To estimate rate of CR/CRh by 4 cycles of treatment
- To estimate overall response rate (ORR) by 4 cycles of treatment. ORR will be defined as CR/CRh/CRi/MLFS/PR for AML and MDS/AML, and CR/CR equivalent/PR/CRL/CRh/HI for MDS or CMML
- To determine duration of response (DOR) of CR/CRh
- To determine overall survival (OS)
Exploratory Objective:
- To characterize the pharmacokinetics (PK) and drug-drug interactions with azole antifungals.
- To characterize pharmacodynamic (PD) biomarkers with monzosertib treatment
- To explore biomarkers of response and resistance
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Phase 1b ESC Arm 1 Treatment - Monzosertib with No Azoles | Experimental | Drug: MonzosertibParticipants may initiate treatment in the inpatient environment, at the discretion of the treating physician. |
| Arm 2: Phase 1b ESC Arm 2 Treatment - Monzosertib with Posaconazole | Experimental | Drug: Monzosertib, Drug: PosaconazoleParticipants may initiate treatment in the inpatient environment, at the discretion of the treating physician. |
| Arm 3: Phase 1b ESC Arm 3 Treatment - Monzosertib with Isavuconazole | Experimental | Drug: Monzosertib, Drug: IsavuconazoleParticipants may initiate treatment in the inpatient environment, at the discretion of the treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients need to be adults ≥18 years with R/R AML, 'MDS/AML', MDS, or CMML, per the ICC 2022 or the WHO 2022 with ≥5% blasts at screening. 6,7
- Relapsed or refractory disease is defined as: patient having received and have progressed or relapsed or intolerant to standard regimens, e.g., as listed in NCCN guidelines, or declined treatment with such therapies.
- "Treated secondary AML" i.e., patients with antecedent hematological disorder, e.g., MDS, CMML, MPD/MPN, who progress to AML despite receiving treatment adequate for AML (per NCCN) for the antecedent hematological disorder, will be eligible due to recognized poor outcomes similar to R/R AML.
- 8,9
- Patients with actionable mutations with available FDA-approved therapies, e.g., FLT3, IDH1/2, menin inhibitors may be enrolled after they have exhausted or ineligible for appropriate lines of FDA approved treatment options.
Key exclusion criteria (12 listed)
- Patient has a white blood cell count > 15 x 10⁹/L. Hydroxyurea, and/or cytarabine use as supportive care is permitted to meet this criterion.10
- Prior use of any cytotoxic chemotherapy, targeted therapy, immunotherapy, or investigational therapies within 2 weeks or 5 half-lives (whichever is shorter), prior to first dose of study treatment. Patients should have recovered from all prior therapy related toxicities. Patients may receive hydroxyurea or cytarabine for control of WBC count during this washout period.
- Patient has uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment.
- Decompensated congestive heart failure, clinically significant, uncontrolled arrhythmia prolonged QT interval corrected for heart rate (QTcF) to greater than 450 msec, or long QT syndrome, or history of Torsades de pointes. Patients with bundle branch block or pacemaker and prolonged QTc interval are permitted after appropriate correction, (e.g., Bogossian formula, or others) or after discussion with the PI and/or cardiologist. Acute respiratory failure, unstable or decompensated pulmonary disease
- Patients with any severe gastrointestinal or metabolic condition or gastric bypass, which could interfere with absorption of oral drug.
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 |
|---|---|---|
| MonzosertibGive by mouth | Drug | Arm 1: Phase 1b ESC Arm 1 Treatment - Monzosertib with No Azoles, Arm 2: Phase 1b ESC Arm 2 Treatment - Monzosertib with Posaconazole, Arm 3: Phase 1b ESC Arm 3 Treatment - Monzosertib with Isavuconazole |
| PosaconazoleAlso: NoxafilGiven by mouth | Drug | Arm 2: Phase 1b ESC Arm 2 Treatment - Monzosertib with Posaconazole |
| IsavuconazoleAlso: Cresemba, Isavuconazonium sulfateGiven by mouth | Drug | Arm 3: Phase 1b ESC Arm 3 Treatment - Monzosertib with Isavuconazole |
Primary outcome
Safety and Adverse Events (AEs).
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
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 21 Aug 2026.
- UT MD Anderson WebsiteLink provided by the sponsor.
Related trials for Acute Myeloid Leukemia (AML)
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Abhishek Maiti, MBBS principal investigator
UT MD 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 1 study testing Monzosertib, Posaconazole and Isavuconazole in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome, 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 14 inclusion and 12 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: opening soon, as of the sponsor's last update on 21 Aug 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 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 Abhishek Maiti, MBBS ((713) 745-3228, amaiti@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse Events (AEs). (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 21 Aug 2026.