HDM201 and Midostaurin (HDMM) in Relapsed/Refractory AML With FLT3mut and TP53wt.

NCT04496999 | Terminated Phase 1

• 1 other identifier: HDMM
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized prospective open-label single-arm clinical phase I trial investigating dose finding, feasibility and safety of the combined treatment of HDM201 and midostaurin in patients with relapsed/refractory acute myeloid leukemia (AML) with FLT3mut applying an accelerated titration design.

Conditions

AML, Adult

Keywords

AML with FLT3-ITD or FLT3-TKD and TP53wt; relapsed/refractory AML

Outcome Measures

Primary Outcomes (1)

• Dose finding

  to identify the incidence of dose limiting toxicities (DLT) at each dose level and to determine the maximum tolerated dose (MTD) of HDM201 and its recommended dose that will be used in a later phase II study (recommended phase II dose; RP2D) when added to midostaurin

  30 days

Secondary Outcomes (5)

• Overall response rate (ORR)

  60 days

• Adverse Events

  33 months

• Progression free survival

  33 months

• Overall survival

  33 months

• Infectious complications of study treatment

  33 months

Study Arms (1)

Midostaurin with HDM201 dose escalation.

EXPERIMENTAL

Midostaurin 50mg bid d1-28 (morning, evening) and HDM201

Drug: HDM201; Drug: Midostaurin

Interventions

HDM201 DRUG

Dose level 0: HDM201 40 mg QD d1,2 (midday)/ Dose level 1: HDM201 40 mg QD d1,2,3 (midday) = Starting dose/ Dose level 2: HDM201 40 mg QD d1,2,3,4,5 (midday)/ Dose level 3: HDM201 60 mg QD d1,2,3,4,5 (midday)/ Dose level 4: HDM201 80 mg QD d1,2,3,4,5 (midday)

Also known as: Dose finding

Midostaurin with HDM201 dose escalation.

Midostaurin DRUG

Midostaurin 50mg bid d1-28 (morning, evening)

Midostaurin with HDM201 dose escalation.

Eligibility Criteria

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

You may qualify if:

• AML with FLT3-ITD or FLT3-TKD and TP53wt.
• Age over 18 years
• Patient must give written informed consent before registration indicating that the patient understands the purpose of the procedures required for the trial and is willing to participate in the trial.
• Patients with relapsed/refractory disease must have morphologic proof (from bone marrow aspirate, smears or touch preps of bone marrow biopsy) of AML with \>= 10% blasts within two weeks (14 days) prior to initiation of therapy.
• Patients must demonstrate one of the following: Relapse after first complete remission or refractory to conventional induction chemotherapy with or without Midostaurin (failure to respond to 1 or more cycles of daunorubicin and cytarabine) or to re-induction.
• Patients with relapse after HSCT (non-preventive) and pretransplant treatment with Midostaurin (FLT3-ITD or FLT3-TKD at diagnosis) or without Midostaurin (acquired FLT3 mutation).
• Laboratory values that indicate adequate organ function assessed locally at the screening visit:
• AST ≤ 3 times ULN
• Alanine aminotransferase (ALT) ≤ 3 times ULN
• Serum total bilirubin ≤ 1.5 times ULN, unless in case of hyperbilirubinemia due to an isolated Gilbert syndrome
• Estimated (by Cockcroft-Gault) creatinine clearance ≥ 30ml/min
• ECOG score performance status 0-2.
• Patients may have received therapy for other malignancies, as long as they have completed therapy at least 6 months prior to study entry.
• Subjects must have a life expectancy of 3 or more months.

You may not qualify if:

• AML with FLT3wt or TP53mut
• Ongoing adverse event drug-induced neuropathy of prior therapy grade ≥2 (according to CTCAE criteria Version 5.0) at registration
• Previous malignancy within 2 years with the exception of adequately treated in situ cervical cancer or localized non-melanoma skin cancer.
• Evidence of ongoing uncontrolled systemic infections.
• Major surgery within 4 weeks prior to trial registration
• Concurrent treatment with other experimental drugs or treatment in a clinical trial within 30 days prior to trial registration.
• Treatment with chemotherapy and radiotherapy within 3 weeks prior to trial registration
• Vaccinated with live, attenuated vaccines within 4 weeks prior to trial registration
• History of stroke or intracranial hemorrhage within 6 months prior to trial registration.
• Clinically significant cardiovascular disease such as congestive heart failure NYHA III or IV (as defined by the New York Heart Association Functional Classification), uncontrolled or symptomatic arrhythmias, unstable angina pectoris, myocardial infarction within 6 months of prior to registration
• Prior solid organ transplantation
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion,
• could impair the ability of the patient to participate in the trial
• could compromise the patient's safety,
• could interfere with the absorption or metabolism of midostaurin or HDM201,

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Departement of Medical Oncology, University Hospital Berne

Bern, 3010, Switzerland

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

siremadlin; midostaurin

Condition Hierarchy (Ancestors)

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

Study Officials

• Thomas Pabst, Prof

  Department of Medical Oncology, University Hospital Bern Switzerland

  STUDY CHAIR

Study Design

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

Model Details: Non-randomized prospective open-label single-arm clinical phase I trial investigating dose finding, feasibility and safety of the combined treatment of HDM201 and midostaurin

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: August 4, 2020
• Study Start: July 13, 2020
• Primary Completion: September 9, 2022
• Study Completion: September 9, 2022
• Last Updated: October 6, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share

Locations

CH (1)