Trial Title:
Phase I Study of Q702 With Azacitidine and Venetoclax for Relapsed or Refractory Acute Myeloid Leukemia
NCT ID:
NCT06445907
Condition:
Acute Myeloid Leukemia
Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Azacitidine
Venetoclax
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Azacitidine
Description:
Given by IV
Arm group label:
Part 1 (Dose Escalation)
Arm group label:
Part 2 (Dose Expansion)
Other name:
5-azacytidine
Other name:
5-aza
Other name:
Vidaza™
Other name:
5-AZC
Other name:
AZA-CR
Other name:
Ladakamycin
Other name:
NSC-102816
Other name:
Azacytidine
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given by PO
Arm group label:
Part 1 (Dose Escalation)
Arm group label:
Part 2 (Dose Expansion)
Other name:
ABT-199
Other name:
GDC-0199
Intervention type:
Drug
Intervention name:
Q702
Description:
Given by PO
Arm group label:
Part 1 (Dose Escalation)
Arm group label:
Part 2 (Dose Expansion)
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.
Detailed description:
Primary Objective:
- To evaluate safety of Q702 and the combination of azacitidine, venetoclax.
Secondary Objectives:
- To estimate rate of CR/CRh/CRi by 4 treatment cycles
- To estimate overall response rate (ORR)
- To estimate rate of MRD negative by 4 treatment cycles
- To estimate overall survival (OS)
- To estimate relapse-free survival (RFS)
Exploratory Objectives:
- To determine the plasma concentration and pharmacokinetic (PK) parameters of Q702
when dosed in combination with azole antifungals in AML patients
- To estimate duration of response (DOR)
- To estimate median time to blood count recovery
- To estimate median time to first response
- To estimate median time to negative MRD
- To study drug-drug interactions with CYP3A4 inhibitor azole antifungals
- Additional response and survival endpoints
- To explore biomarkers of response, pathway engagement, and resistance
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants 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
2. Participants ≥18 years with R/R AML or R/R MDS/AML, other than acute promyelocytic
leukemia (APL), with no available standard treatment options.
3. 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 venetoclax with HMA/LDAC +/- other agents
- 4 cycles of HMA alone
- 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.
4. ECOG PS 0 to 1
5. Participants 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 ("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.
6. Participants 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.
7. Participants 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
8. Adequate hepatic function (total bilirubin ≤ 1.5 x upper limit of normal (ULN)
unless increase is due to Gilbert's disease, and AST and/or ALT ≤ 2 x ULN).
9. Adequate renal function with creatinine clearance ≥ 45 mL/min calculated by the
Cockcroft-Gault formula or MDRD equation or measured by 24-hour urine collection.
10. 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.
a. 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.
b. 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. c. Men treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study, for the duration of study participation,
and 4 months after completion of treatment.
11. Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
1. Participants with t(15;17) karyotypic abnormality.
2. Participant has a white blood cell count > 15 x 10⁹/L. Hydroxyurea, and/or
cytarabine (up to 2 g/m2 total) used as supportive care is permitted to meet this
criterion prior to enrollment.
3. Prior use of any cytotoxic chemotherapy, targeted therapy, radiation therapy,
immunotherapy, or other clinical trial therapies within 2 weeks, prior to first dose
of study treatment. Participants should have recovered from all prior therapy
related toxicities. Participants may receive hydroxyurea or cytarabine for control
of WBC count during this washout period.
4. Participants with known symptomatic or uncontrolled CNS leukemia.
5. Participant has systemic fungal, bacterial, viral or other infection that is
exhibiting ongoing signs/symptoms related to the infection without improvement
despite appropriate treatment.
6. 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:
1. 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 pre-existing retinopathy or a condition with the
potential to cause a predisposition to drug-induced retinopathy.
2. Participants with only one assessable eye and no evidence of pre-existing
retinopathy may be allowed at the discretion of the principal investigator.
7. Participants with known acute or chronic liver disease, cirrhosis, hepatic steatosis
with elevated liver function tests or elevated LFTs of unknown etiology.
8. 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.
9. Decompensated congestive heart failure, hypokalemia, prolonged QT interval corrected
for heart rate (QTc) (as calculated using Fridericia's formula) to greater than 450
msec for males, or to greater than 470 msec for females or long QT syndrome, or
history of Torsades de pointes.
10. Participants with any severe gastrointestinal or metabolic condition which could
interfere with the absorption of oral study medications as determined by the
investigator.
11. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection with detectable viral
DNA or RNA, respectively, or known HIV or HTLV-1 infection.
12. 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.
13. 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. Participants 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.
14. Major surgery within 4 weeks prior to screening or a major wound that has not fully
healed.
- Participants under legal protection measure (guardianship, trusteeship or
safeguard of justice) and/or uncontrolled psychiatric comorbidities, ongoing
illicit substance abuse, any impairment or unwillingness to comply with the
treatments, follow-up, requirements and procedures of this clinical trial.
15. A known hypersensitivity or severe allergy to study drug components or diluents
16. Nursing women, women of childbearing potential (WOCBP) with positive urine or serum
pregnancy test, or WOCBP who are not willing to maintain adequate contraception.
17. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Contact:
Last name:
Abhishek Maiti, MBBS
Phone:
713-745-3228
Email:
amaiti@mdanderson.org
Investigator:
Last name:
Abhishek Maiti, MBBS
Email:
Principal Investigator
Start date:
November 29, 2024
Completion date:
July 1, 2028
Lead sponsor:
Agency:
M.D. Anderson Cancer Center
Agency class:
Other
Collaborator:
Agency:
Qurient Co., Ltd.
Agency class:
Industry
Source:
M.D. Anderson Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06445907
http://www.mdanderson.org