MRD-guided Treatment in NPM1mut AML Patients

NCT03769532 | Terminated Phase 2 DMC

• 1 other identifier: TUD-PEMAZA-068
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 10

Brief Summary

Evaluation the safety and efficacy of Pembrolizumab (PEM) when administered in combination with standard Azacitidine (AZA) in nucleophosmin (NPM1) mutated AML patients with molecular relapse defined by the presence of measurable residual disease (MRD).

Conditions

Acute Myeloid Leukemia

Keywords

AML; NPM1mut; molecular relapse; pembrolizumab; azacitidine

Outcome Measures

Primary Outcomes (1)

• Proportion of event-free patients

  Events are: * First hematological relapse after start of combined therapy * Death from any cause * AML-treatment other than Pembrolizumab and Azacitidine or hypomethylating agents only

  after 24 weeks of combination treatment (i.e. after up to 6 cycles of AZA for 7 days every 4 weeks and up to 8 PEM infusions every 3 weeks)

Secondary Outcomes (4)

• Overall survival (OS)

  through study completion, an average of 1 year

• Proportion of event-free patients

  after 12 weeks of combined therapy

• Treatment-related mortality

  during 24 weeks of combined therapy

• Course of MRD-burden measured as quantitative NPM1/Abelson murine leukemia viral oncogene homolog 1 (ABL) ratio

  through study completion, an average of 1 year

Study Arms (1)

Pembrolizumab + Azacitidine

EXPERIMENTAL

Pembrolizumab (IMP): 200 mg i.v. (fixed dose) / Azacitidine (SOC): 75 mg/m2 s.c. maximum duration of treatment: up to 24 weeks

Drug: Pembrolizumab; Drug: Azacitidine

Interventions

Pembrolizumab DRUG

Pembrolizumab (IMP): 200mg i.v. (fixed dose), every 3 weeks (Q3W), 8 doses

Also known as: PEM, Keytruda®

Pembrolizumab + Azacitidine

Azacitidine DRUG

Azacitidine (SOC): 75 mg/m2 s.c., day 1-7 every 4 weeks (Q4W), 6 cycles

Also known as: AZA, Vidaza®

Pembrolizumab + Azacitidine

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Age ≥18 years
• Patients with NPM1mut AML in complete morphologic remission after conventional chemotherapy (anthracycline ± cytarabine based)
• Detectable measurable residual disease (MRD) indicating imminent hematological relapse (NPM1mut MRD ratio \>1%, confirmed by central lab)
• Patients who are not eligible for immediate allogeneic hematopoietic stem cell transplantation
• Patients who are not eligible to undergo alternative intensive treatment
• Intended AZA therapy for molecular relapse
• Eastern cooperative oncology Group (ECOG) performance status of 0 or 1
• Demonstrate adequate organ function as defined by protocol, all labs should be performed within the screening period.
• Negative pregnancy test in women of childbearing potential (negative urine or serum pregnancy within 3 days prior to receiving study treatment). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential (Section 5.9.2) must be willing to use an adequate method of contraception as outlined in Section 5.9.2 - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects with procreative capacity (Section 5.9.2) must agree to use an adequate method of contraception as outlined in Section 5.9.2- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Prior allogeneic hematopoietic stem cell transplantation
• Treatment with any investigational drug within 4 weeks to study therapy or less than 5 half-lives preceding the first dose of trial medication, whichever is longer.
• Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or no recovering (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or no recovering (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Prior treatment with an anti-programmed cell death protein (anti PD-1, anti PD-L1 or anti PD-L2 agent).
• Known hypersensitivity to any of the drugs within this study, their constituents or to drugs with similar chemical structure.
• Receiving immunosuppressive therapy within 7 days prior to the first dose of trial medication.
• Known history of active Bacillus Tuberculosis (TB).
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Known history of, or any evidence of active, non-infectious pneumonitis.
• Liver cirrhosis or malignant liver tumor.
• Known severe congestive heart failure, incidence of clinically unstable cardiac or pulmonary disease.

Sponsors & Collaborators

• Technische Universität Dresden: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Klinikum Chemnitz

Chemnitz, 09116, Germany

Location

Universitätsklinikum Dresden

Dresden, 01307, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Kliniken Maria Hilf

Mönchengladbach, 41063, Germany

Location

Klinikum r. d. I.

München, 81675, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Robert-Bosch-Krankenhaus

Stuttgart, 70376, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

pembrolizumab; Azacitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jan Moritz Middeke, MD

  Technische Universität Dresden (TUD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 7, 2018
• Study Start: August 21, 2019
• Primary Completion: February 13, 2025
• Study Completion: February 13, 2025
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)