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TEAM-Trial: Targeting Epigenetic Therapy Resistance in AML With Bortezomib

NCT04173585 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 50

Last updated 2023-03-27

No results posted yet for this study

Summary

The long-term outcome of patients with acute myeloid leukemia (AML) remains poor, with less than 30% of patients achieving long lasting remission or cure. This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy. In patients with refractory/relapsed AML hematopoietic cell transplantation (allo-HCT) is currently the only treatment option offering a prospect of cure but outcome is heavy influenced by the remission status before allo-HCT. Therefore, patients are typically treated with salvage regimens based on high dose cytarabine (HiDAC) combined with mitoxantrone, fludarabine or idarubicin. Nevertheless, the remission rates remain poor and currently there is no accepted standard salvage regimen. Recent studies indicate that combination chemotherapy including HiDAC and gemtuzumab ozogamicin (GO) at a dose of 3 mg/m² leads to improved response rates in refractory AML.

Proteasome inhibition with bortezomib appears to be a promising treatment strategy to restore chemo-sensitivity via EZH2 stabilisation.

This study aims at improving response rates in refractory/ relapsed AML by combining high dose cytarabine, gemtuzumab ozogamicin (GA) and bortezomib (B).

During this phase II study efficacy of B-GA is assessed in comparison to matched historical controls using the Matched Threshold Crossing (MTC)-approach. If results are promising, a subsequent randomized phase III study is intended to assess the efficacy of GA with or without bortezomib.

Conditions

Interventions

DRUG

Bortezomib

Bortezomib is a small molecule dipeptide binding the catalytic site of the 26 S proteasome. It acts as a potent, reversible, and specific inhibitor of proteasomes and thus impairs the degradation of ubiquitinated proteins. It has demonstrated anti-neoplastic activity in myeloma and lymphoma. It is approved and widely used in multiple myeloma both for first line treatment and relapsed patients.

DRUG

Gemtuzumab Ozogamicin

Gemtuzumab Ozogamicin is a monoclonal antibody directed against the myeloid surface antigen CD33. The antibody is linked to calicheamicin which serves as cytotoxic agent. For years, gemtuzumab ozogamicin has been tested in clinical AML trials. Though withdrawn from the US market in 2010, FDA approval was granted in September 2018, EU approval in April 2018 based on encouraging results from recent clinical trials using enhanced dosing schedules.

Sponsors & Collaborators

  • National Center for Tumor Diseases, Heidelberg

    collaborator OTHER

  • University Hospital Heidelberg

    lead OTHER

Principal Investigators

  • Carsten Müller-Tidow, Prof., MD · Medical Director of Internal Medicine V, University Hospital Heidelberg

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
100 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-10-22
Primary Completion
2023-02-28
Completion
2023-03-24

Countries

  • Germany

Study Locations

More Related Trials

Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04173585 on ClinicalTrials.gov