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

NCT06522373 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0177NCI-2024-06176
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

To learn if MT-0169 is safe to give to patients with AML or T-ALL. The effects of this drug will also be studied.

Conditions

Leukemia

Outcome Measures

Primary Outcomes (1)

• 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 (4)

Escalation Adults: MT-0169

EXPERIMENTAL

Drug: MT-0169

Escalation Pediatrics: MT-0169

EXPERIMENTAL

Drug: MT-0169

Expansion Adults: MT-0169

EXPERIMENTAL

Drug: MT-0169

Expansion Pediatrics: MT-0169

EXPERIMENTAL

Drug: MT-0169

Interventions

MT-0169 DRUG

Given by Vein (IV)

Escalation Adults: MT-0169; Escalation Pediatrics: MT-0169; Expansion Adults: MT-0169; Expansion Pediatrics: MT-0169

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients need to be ≥ 12 years of age.
• ECOG performance status of o to 2.
• 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
• 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.
• 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.
• 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.
• 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.
• Patients relapsing with persistent or new TP53 mutation will be eligible irrespective of CR1 duration.
• Older/unfit patients who relapse on venetoclax based maintenance regimen will be eligible irrespective of CR1 duration.
• 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
• Patients with AML will be eligible if they have MRD ≥ 0.1% using multiparametric flow cytometry assay.
• 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
• Patients in 2nd or higher cCR for AML or T-ALL will be eligible after at least one cycle of salvage therapy.
• Patients with MRD relapse after allo-SCT or during consolidation or maintenance therapy will be eligible.

You may not qualify if:

• Patient has a white blood cell count \> 10 x 10⁹/L. Hydroxyurea, and/or cytarabine (up to 2 g/m2 total) used as supportive care is permitted to meet this criterion.
• 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.
• Patients with the following cardiovascular conditions:
• Congestive heart failure, NYHA class ≥II, cardiomyopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction, clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening, (stable medical therapy for \> 6 months is acceptable)
• Clinically significant uncontrolled hypertension at the time of screening,
• Patients with a history of documented pericarditis (any CTCAE grade) or pericardial effusions of at least CTCAE Grade 3 within 3 months before the start of treatment with MT-0169.
• Received chemotherapy with anthracycline agents at the doxorubicin equivalent cumulative dose (sum for all agents combined) of 450 mg/m2 body surface area, or a lower total doxorubicin equivalent cumulative dose that, in the opinion of the Investigator, would increase the risk of cardiomyopathy in this study.
• i. For patients who have received a cumulative dose of an anthracycline of more than 300 mg/m2 , approval must first be obtained from the Medical Monitor
• Patients with a history of mediastinal irradiation.
• Prior use of any cytotoxic chemotherapy, targeted therapy, antibody-drug conjugates, immunotherapy, or other investigational therapies within 2 weeks or 5 half-lives, whichever is shorter, prior to starting MT-0169. All prior therapy related toxicities should have resolved to grade ≤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 ("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.
• Known active hepatitis B (HBV) or Hepatitis C (HCV) infection with detectable viral DNA or RNA, respectively, or known HIV 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.
• Any previous or concomitant malignancy, except when the patient has completed definitive curative-intent treatment with chemotherapy and/or surgery and/or radiotherapy at least 3 months 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, imaging, and/or cytology/pathology, e.g., non-melanoma skin cancers, or a carcinoma in-situ, e.g., ductal carcinoma in situ, urothelial cancer, cervical cancer, localized prostate cancer, pre-cancerous colon polyp, etc.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Abhishek Maiti, MBBS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: July 22, 2024
• First Posted: July 26, 2024
• Study Start: October 21, 2024
• Primary Completion: October 21, 2024
• Study Completion: October 21, 2024
• Last Updated: May 15, 2026

Record last verified: 2026-05