Recruiting
Phase 1
A Phase Ib Study of Rezatapopt in Combination With Azacitidine in Patients With TP53Y220C Mutant Myeloid Malignancies (Acute Myeloid Leukemia or Myelodysplastic Syndrome)
About this study
A non-randomized phase Ib study of PC14586 (PMV therapeutics) in patients diagnosed with TP53Y220C-mutant myeloid malignancies, including AML and MDS.
- Condition
- Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Tested
- Azacitidine, Rezatapopt
- Sponsor
- M.D. Anderson Cancer Center
Who can join
- Age
- 18 years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
Inclusion 24
- Minimum age: 18 years
- Study condition: Myelodysplastic Syndrome, Acute Myeloid Leukemia
- Patient is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
- Patient has relapsed or primary refractory AML or MDS
- Any other comorbidity that per the investigator renders a patient inappropriate for intensive chemotherapy.
- Patients with MDS must be classified as MDS-IB1 or IB2 as per WHO 2022 criteria32
- TP53Y220C mutation confirmed by CLIA-approved local testing with a variant allele frequency \>2%.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
- Patient has adequate organ function defined as:
- Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x ULN, unless considered due to leukemic organ involvement.
- Serum total bilirubin ≤ 1.5 x ULN. Higher levels are acceptable if these can be attributed to ineffective erythropoiesis, leukemia organ involvement or Gilbert\'s syndrome.
- Serum creatinine \< 2 x ULN or creatinine clearance \> 40 mL/min based on validated glomerular filtration rate (GFR) estimation (Cockcroft-Gault, CKD-epi, or MDRD equations).
- Females of childbearing potential may participate provided they have a negative serum or urine pregnancy test at screening and a negative serum OR urine pregnancy test within 72 hours of starting on treatment.
- They also must agree to either abstain from sexual intercourse or use two forms of a highly effective method of contraception while on study and up to 3 months after the last dose of the study drug.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 14 days prior to study entry and for the duration of study participation.
- This includes all female patients between the onset of menses and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
- Postmenopausal (no menses in greater than or equal to 12 consecutive months). History of hysterectomy or bilateral salpingo-oophorectomy. Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
- 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.
- 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 3 months after completion of investigational agent administration.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion 12
- Patient has received prior chemotherapy, targeted therapy, immunotherapy, or treatment with an investigational anticancer agent within 14 days or 5 half-lives (if half-life is known), whichever is shorter, before receiving their first dose of study drug.
- Patient has received radiotherapy within 14 days.
- Patients with acute promyelocytic leukemia
- Subject has immediate life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- Patients with active, uncontrolled leukemia involvement of the CNS
- Subject has known active viral infection with human immunodeficiency virus (HIV), or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Subject is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- Subject has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment).
- Patient has any unresolved toxicities from prior anti-cancer therapy greater than Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior chemotherapy induced neuropathy.
- Patient has had major surgery within 2 weeks prior to the planned start of study treatment.
- Female subject who is pregnant or lactating.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to azacitidine, rezetapopt or other agents used in study.
Where
2 sites, 2 recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Moffitt Cancer Center
Tampa, Florida, United States
Contact
-
Courtney DiNardo, MD
(713) 794-1141 cdinardo@mdanderson.org
Potential match only. Final eligibility is determined by the study team.