Phase I Trial of MT-0169 in CD38+ Acute Leukemia With Relapsed/Refractory or Measurable Residual Disease

Recruitment & Eligibility

Status: Not yet recruiting

Sex: All

Target Recruitment: 52

Inclusion Criteria

Inclusion Criteria: 1. Patients need to be = 12 years of age. 2. ECOG performance status of o to 2. 3. Patients need to have a confirmed diagnosis of T-ALL, or AML, MDS/AML, (10% to 19% blasts), or mixed or biphenotypic leukemia, per the International Consensus Classification or the WHO classification.40,41 4. Patients need to have either relapsed or refractory disease: T-ALL, AML, MDS/AML, MPAL, biphenotypic leukemia; or patients with AML or T-ALL in CR/CRi/CRh with measurable residual disease (MRD), and no available standard or approved treatment options. Patients with MPAL or biphenotypic leukemia will only be eligible during the dose escalation phase. 5. Patients will need to have positive CD38 expression on leukemia cell population for dose escalation cohort and CD38 expression =20% on leukemia cell population by flow cytometry or IHC for dose expansion cohorts as assessed by standard of care flow cytometry. 6. 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 c. Patients with AML must have received appropriate prior therapy in order for patient to be deemed relapsed or refractory, including 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.42,43 ii. At least 1 cycle of intensive induction chemotherapy with venetoclax, e.g., 7 + 3 or CPX-351 with venetoclax 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 v. 4 cycles of HMA-based regimen d. Patients with T-ALL should have received at least 1 cycle of a standard or appropriate frontline regimen per NCCN or ELN2023 guidelines for ALL.44,45 e. Patients with mixed or biphenotypic leukemia should have received one AML or ALL type regimen as mentioned above f. Pediatric patients need to have R/R disease after at least one line of standard pediatric frontline regimen. 7. For patients in first relapse, the dose escalation cohort will only enroll patients in early first relapse, i.e., first remission duration of =12 months. 1. Patients relapsing with persistent or new TP53 mutation will be eligible irrespective of CR1 duration. 2. Older/unfit patients who relapse on venetoclax based maintenance regimen will be eligible irrespective of CR1 duration. 8. Patients without overt relapse but positive measurable residual disease (MRD) with a response status of composite CR (cCR = CR/CRi/CRh, i.e., <5% blasts) will be eligible for the trial 1. Patients with AML will be eligible if they have MRD = 0.1% using multiparametric flow cytometry assay. 2. Patients with T-ALL will be eligible if they have MRD =0.01% by multiparametric flow cytometry, or PCR/NGS (i.e., = 100 residual clonal cells per million nucleated cells evaluated by T-cell repertoire sequencing by PCR and/or NGS [commercial Adaptive clonoSEQ assay]).7,11 3. Patients in 2nd or higher cCR for AML or T-ALL will be eligible after at least one cycle of salvage therapy. 4. Patients with MRD relapse after allo-SCT or during consolidation or maintenance therapy will be eligible. 5. Patients with AML in first remission cCR will be eligible if they have adverse risk AML per ELN2022 and must have received at least, i. 1 cycle of intensive induction and 1 cycle of consolidation chemotherapy with intermediate or high-dose cytarabine based regimen,46 or ii. 4 cycles of venetoclax-based lower intensity regimen containing HMA or LDAC, due to know adverse prognosis of such patients,22,23,47,48 or iii. 4 cycles of frontline HMA-based regimen (i.e., CR1), or f. Patients with T-ALL in first remission (CR1) will be eligible if they have positive MRD after 2 cycles of frontline therapy per NCCN or ELN2023 guidelines for ALL.44,45 9. Patients relapsing after allo-SCT may be eligible if they have recovered from all transplant-related toxicities, with no more than grade 1 chronic GVHD. 10. Patients with actionable mutations with FDA-approved therapies, e.g., FLT3, IDH1/2 inhibitors may be enrolled after they have received at least one appropriate line of available FDA approved treatment option. 11. Adequate hepatic function (direct bilirubin = 2 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 direct bilirubin or AST and/or ALT = 3 x ULN will be considered eligible.) 12. Adequate renal function with creatinine clearance = 30 mL/min calculated by the Cockcroft-Gault formula or measured by 24-hour urine collection 13. Patients must meet the following cardiovascular parameters. 1. Left ventricular ejection fraction (LVEF) = 50 % by echocardiogram. 2. QT interval with Fridericia correction method (QTcF) on screening electrocardiogram, defined as QTcF of =450 ms in males or =470 ms in females. 14. The effects of this agent 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. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy #CLN1114; this applies to patients enrolled at MDA only. External participating sites will follow their own institutional policies/SOP.) 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: - 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. 15. 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, per