A study to evaluate the safety and efficacy of mebendazole in combination with low-dose Ara-C in elderly patients with relapsed/refractory acute myeloid leukemia (MAIL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Medical Center Hamburg-Eppendorf

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 21 Aug 2025

Decision date (initial)

2024-10-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

University Medical Centre Hamburg-Eppendorf

External identifiers

EU CT number

2024-518363-36-00

EudraCT number

2019-002838-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Others, Pharmacodynamic, Dose response, Efficacy, Safety, Pharmacogenetic

Phase I:

• Studying the safety of the combination of low-dose Ara-C and mebendazole in elderly patients ≥ 70 years with relapsed/ refractory AML
• Establishing a safe and biologically relevant dose of mebendazole in combination with low dose Ara-C

Phase II:

• Determination of the combined rate of complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi) within three months

Secondary objectives 5

1. Phase I: Performing limited PK and PD analyses of mebendazole
2. Phase II: Determination of Event-free and Overall survival
3. Phase II: Studying effects of mebendazole on the hedgehog pathway in patients under treatment
4. Phase II: Correlation of mutational status with response to mebendazole therapy and clonal evolution
5. Phase II: Performing minimal residual disease assessment (MRD) in responding patients by NGS

Conditions and MedDRA coding

relapsed/refractory acute myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Cytological or histological diagnosis of AML with the exception of promyelocytic leukemia (AML M3)
2. Relapsed/refractory disease after standard therapy
3. Blast concentration in peripheral blood of > 1000/μl
4. Men and women aged >70 years, ineligible for intensive treatment (standard dose)
5. Ability to swallow and retain oral medication, no known malabsorption syndrome, adequate organ function
6. Ability to understand and provide signed informed consent

Exclusion criteria 7

1. Persistence of toxicity of prior chemotherapy above grade 1
2. Prior treatment with low dose Ara-C
3. Treatment with any investigational agents within a clinical trial in the last four weeks
4. Central nervous system (CNS) disease
5. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
6. Intolerance against components of mebendazole or cytarabine formulations (especially E110)
7. Acute or chronic liver diseases with elevated liver enzymes above grade 1

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Phase I: Determination of MTD by recording frequency and severity of adverse events graded by CTCAE v5.0.
2. Phase I: Determination of a biologically relevant Phase II regimen
3. Phase II: Combined rate of complete remission (CR) and morphologic complete remission with incomplete blood count recovery (CRi) within three months

Secondary endpoints 6

1. Phase I: PD parameters such as a modified PIA assay
2. Phase I: PK analysis
3. Phase II: Determination of GLI1/2 levels in circulating AML cells before and under treatment
4. Phase II: Determination of Event free and Overall survival
5. Phase II: Determination of subclonal response by NGS
6. Phase II: Performing minimal residual disease assessment (MRD) in responding patients by NGS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Medical Center Hamburg-Eppendorf

Sponsor organisation

University Medical Center Hamburg-Eppendorf

Address

Martinistrasse 52, Eppendorf Eppendorf

City

Hamburg

Postcode

20246

Country

Germany

Scientific contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Center for Oncology, UKE, Executive senior physician

Public contact point

Organisation

University Medical Center Hamburg-Eppendorf

Contact name

Center for Oncology, UKE, Executive senior physician

Third parties 3

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications