Phase I Study of Q702 With Azacitidine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia

NCT06445907 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0178NCI-2024-04788
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

To learn about the safety and tolerability of the drug combination of Q702, azacitidine, and venetoclax when given to participants with relapsed/refractory AML.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

  Through study completion; an average of 1 year.

Study Arms (2)

Part 1 (Dose Escalation)

EXPERIMENTAL

Participants receive Q702 orally (PO) once daily (QD) on days 1-7 and 15-21 of each cycle. Azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle and venetoclax PO QD on days 1-21 or days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo collection of blood samples and bone marrow aspiration and/or biopsy throughout the trial.

Drug: Azacitidine; Drug: Venetoclax; Drug: Q702

Part 2 (Dose Expansion)

EXPERIMENTAL

Participants receive Q702 orally (PO) once daily (QD) on days 1-7 and 15-21 of each cycle. Azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7 of each cycle and venetoclax PO QD on days 1-21 or days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also undergo collection of blood samples and bone marrow aspiration and/or biopsy throughout the trial.

Drug: Azacitidine; Drug: Venetoclax; Drug: Q702

Interventions

Azacitidine DRUG

Given by IV

Also known as: 5-azacytidine, 5-aza, Vidaza™, 5-AZC, AZA-CR, Ladakamycin, NSC-102816, Azacytidine

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Venetoclax DRUG

Given by PO

Also known as: ABT-199, GDC-0199

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Q702 DRUG

Given by PO

Part 1 (Dose Escalation); Part 2 (Dose Expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients need to have a confirmed diagnosis of AML, or MDS/AML with 10% to 19% blasts, per the International Consensus Classification 2022 or the WHO 2022 classification.23,24
• Patients .18 years with R/R AML or R/R MDS/AML, other than acute promyelocytic leukemia (APL), with no available standard treatment options.
• Relapsed or refractory disease defined by standard criteria as follows:
• a. Relapsed: Bone marrow blasts .5%, reappearance of blasts in the blood, or development of extramedullary disease following achievement of CR/CRi/MLFS b. Refractory: Failure to achieve CR/CRi/MLFS following initial treatment, with evidence of persistent leukemia by blood and/or bone marrow evaluation with blasts .5% c. Appropriate prior therapy in order for patient to be deemed relapsed or refractory include any of the following: i. At least 1 cycle of purine analogue containing intensive induction chemotherapy regimen, e.g., FLAG-Ida, CLIA or CLAG-M or similar regimens with or without venetoclax.25,26 ii. At least 1 cycle of intensive induction chemotherapy with venetoclax, e.g., 7 + 3 or CPX-351 with venetoclax or similar regimens iii. At least 2 cycles of intensive induction chemotherapy such as 7 + 3 or 5 + 2 or similar regimens without venetoclax iv. 2 cycles of BCL2 inhibitor with HMA/LDAC +/- other agents v. 4 cycles of HMA-based regimen without BCL2 inhibitor
• \- Younger/fit patients (\<60 years) in first relapse following intensive chemotherapy, will only be eligible if the first remission (CR1) duration was .12 months.
• d. Patients relapsing with persistent or new TP53 mutation will be eligible irrespective of CR1 duration. e. Older/unfit patients who relapse on HMA + venetoclax based maintenance regimen will be eligible irrespective of CR1 duration.
• ECOG PS 0 to 1
• Patients relapsing after allo-SCT may be eligible if they have recovered from all transplant related toxicities and are off all immunosuppression, with no more than grade 1 chronic GVHD. Physiologic ( greplacement h) 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.
• Patients with actionable mutations with available FDA-approved therapies, e.g., FLT3, IDH1/2 inhibitors may be enrolled after they have exhausted appropriate lines of FDA approved treatment options.
• Patients with antecedent hematological disorder (AHD), e.g., aplastic anemia, myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) or myeloproliferative disorder or neoplasm (MPD or MPN) who have previously received a regimen appropriate for AML for the antecedent hematological disorder, as described above, and have progressed to AML, will be eligible for the dose escalation and salvage dose expansion cohorts. This is due to recognized poor outcomes in such patients with "treated secondary AML".27,28
• Adequate hepatic function (total bilirubin . 1.5 x upper limit of normal (ULN), and AST and/or ALT . 2 x ULN). Patients with Gilbert disease will be eligible with total bilirubin . 4.5 mg/dL.
• Adequate renal function with creatinine clearance . 60 mL/min calculated by the Cockcroft- Gault formula or MDRD equation or measured by 24-hour urine collection.
• 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.
• 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.

You may not qualify if:

• Patients with t(15;17) karyotypic abnormality.
• Patient has a white blood cell count \> 15 x 10./L. Hydroxyurea, and/or cytarabine (up to 2 g/m2 total) used as supportive care is permitted to meet this criterion prior to enrollment.
• Prior use of any cytotoxic chemotherapy, targeted therapy, radiation therapy, immunotherapy, or other clinical trial 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.
• Patients with known symptomatic or uncontrolled CNS leukemia.
• Patient has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate treatment.
• Active ophthalmological disorders, e.g., retinal pigment epithelium (RPE)/photoreceptor disorders such as retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular degeneration. Exceptions:
• Mild blurry vision, either age-related or due to ocular or systemic disorder (e.g., diabetes, dry eyes, cataracts, uncorrected refraction abnormality) may be allowed at the discretion of an ophthalmologist if deemed as not constituting evidence of preexisting retinopathy or a condition with the potential to cause a predisposition to druginduced retinopathy.
• Patients with only one assessable eye and no evidence of pre-existing retinopathy may be allowed at the discretion of the principal investigator.
• Any known and active neurological disorder with residual neurological deficit or requiring pharmacotherapy.
• Patients with known acute or chronic liver disease, cirrhosis, hepatic steatosis with elevated liver function tests or elevated LFTs of unknown etiology.
• Active and uncontrolled comorbidities including decompensated congestive heart failure NYHA class III/IV, clinically significant, uncontrolled arrhythmia, acute respiratory failure, unstable or decompensated pulmonary disease, as judged by the treating physician.
• Decompensated congestive heart failure, hypokalemia, prolonged QT interval corrected for heart rate (QTc) to greater than 470 msec or long QT syndrome, or history of Torsades de pointes. Appropriate corrections may be applied for patients with bundle branch block.
• Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications as determined by the investigator.
• Known active hepatitis B (HBV) or Hepatitis C (HCV) infection with detectable viral DNA or RNA, respectively, or known HIV or HTLV-1 infection.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Qurient Co., Ltd.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Abhishek Maiti, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abhishek Maiti, MBBS

CONTACT

(713) 745-3228; amaiti@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 6, 2024
• Study Start: February 12, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: February 24, 2026

Record last verified: 2025-11

Locations

US (1)