Treatment of imminent hematological relapse as defined by measurable residual disease in patients with nucleophosmin (NPM1)-mutated acute myeloid leukemia (AML) using pembrolizumab and azacitidine

Phase 1

• Conditions: Patients with NPM1mut AML >= 18 years in CR presenting with MRD after conventional chemotherapy; MedDRA version: 20.0 Level: LLT Classification code 10000886 Term: Acute myeloid leukemia System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004110-25-DE
• Lead Sponsor: Technische Universität Dresden

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-16
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 28

Inclusion Criteria

- Signed informed consent
- Age =18 years
- Patients with NPM1mut AML in complete morphologic remission after conventional chemotherapy (anthracyclines ± cytarabin based)
- Detectable measurable residual disease (MRD) indicating imminent hematological relapse (NPM1mut status >1%)
- 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
- ECOG performance status of 0 or 1
- Adequate organ function as defined by protocol
- No allogeneic stem cell transplantation (allo SCT) within 5 years prior to study treatment
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 3 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential must be willing to use an adequate method of contraception (Section 5.9.2), for the course of the study through 120 days after the last dose of study medication
- Male subjects with procreative capacity must agree to use an adequate method of contraception (Section 5.9.2), starting with the first dose of study therapy through 120 days after the last dose of study therapy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 14
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 14

Exclusion Criteria

- Current treatment with any investigational drug or within 4 weeks or less than 5 half-lives preceding the first dose of trial medication, whichever is longer
- Known hypersensitivity to any of the drugs used or their constituents or to drugs with similar chemical structure
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Known history of active TB (Bacillus Tuberculosis)
- Anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (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 who has not recovered (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.
- Completed 24 months of uninterrupted treatment with pembrolizumab or 35 administrations of study medication, whichever is later
- 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
- Active 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
- Severe hepatic impairment (AST and ALT may not exceed three times the normal) or liver cirrhosis or malignant liver tumor
- Dialysis dependent renal dysfunction
- Known severe congestive heart failure, incidence of clinically unstable cardiac or pulmonary disease
- Active infection requiring systemic therapy
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participat

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified