MRD-guided Treatment in NPM1mut AML Patients

• Status: Recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Technische Universität Dresden
• Collaborator: Merck Sharp & Dohme Corp.
• Treatments: Azacitidine; Pembrolizumab

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• 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 participate, in the opinion of the treating investigator.

• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment

• Known Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

• Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., Hepatitis C virus (HCV) RNA [qualitative] is detected).

• Live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.