A Dose Exploration Study With Birabresib (MK-8628) in Participants With Selected Hematologic Malignancies (MK-8628-005)
Condition: AML Including AML de Novo and AML Secondary to MDS; DLBCL
MeSH terms: Hematologic Neoplasms
Intervention: Birabresib Dose 20 mg
Intervention description: Administered as an oral capsule twice a day for 21 consecutive days per cycle.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study to determine the recommended dose of birabresib (MK-8628) for further studies
      in participants with acute myeloid leukemia (AML) including AML de novo and AML secondary to
      myelodysplastic syndrome (MDS) and in participants with diffuse large B cell lymphoma
      (DLBCL). The recommended dose will be established by evaluating dose limiting toxicity (DLT),
      safety, tolerability, and early efficacy signals.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of AML (AML de novo and post-MDS) or DLBCL

          -  AML participants must have the following malignancy criteria: measurable and evaluable
             disease per tumor response criteria; ≥ 5% bone marrow blasts without alternate
             causality; and > 90 days since allogeneic stem cell transplantation relapse in
             participants relapsing after transplant

          -  AML participants who are Philadelphia chromosome positive must have received ≥ 2 lines
             of therapy, including 2 bcr-abl tyrosine-kinase (TK) inhibitors (among imatinib,
             nilotinib and dasatinib), or only 1 line including 1 TK inhibitor if the
             relapse/refractoriness is associated with the detection of a resistance mutation to
             these inhibitors

          -  AML participants < 60 years old must be in second or further relapse or relapsing
             after allogeneic stem cell transplantation regardless of number of relapses

          -  AML participants ≥ 60 years old in first relapse with a disease-free interval < 12
             months, or further relapse. First relapse is also applicable to AML post-MDS patients
             who have received prior treatment for MDS, but have not received prior treatment for
             AML.

          -  DLBCL participants must have the following malignancy criteria: measurable and
             evaluable disease per tumor response criteria and ≥ 1 tumor mass that is ≥ 15 mm (long
             axis of lymph node) or ≥ 10 mm (short axis of lymph node or extranodal lesions) on
             spiral CT scan; failed 2 standard lines of therapy (at least one containing an
             anti-CD20 monoclonal antibody), or for whom such treatment is contraindicated.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1

          -  An interval of ≥3 weeks since chemotherapy (≥ 6 weeks for nitrosoureas or mitomycin
             C), immunotherapy, hormone therapy or any other anticancer therapy or surgical
             intervention resection, or ≥3 half-lives for monoclonal antibodies, or ≥ 5 half-lives
             for other non-cytotoxic agents (whichever is longer)

          -  Female participants must not be pregnant (negative urine or serum human chorionic
             gonadotropin test within 72 hours of study start)

          -  Female and male participants of reproductive potential must agree to use adequate
             contraception starting from the first dose of trial treatment through 90 days after
             the last dose of study medication

        Exclusion Criteria:

          -  Known primary central nervous system (CNS) malignancy or symptomatic or untreated CNS
             metastases

          -  History of prior or concomitant malignancies within 3 years of study start

          -  Has other serious illness or medical condition, such as active infection, unresolved
             bowel obstruction, psychiatric disorders, or cerebrovascular accident within 1 year of
             study start

          -  Known history of human immunodeficiency virus (HIV) and/or active Hepatitis B or C
             infections

          -  Has one of the following cardiac-related conditions: Congestive heart failure; angina
             pectoris; myocardial infarction (within 1 year of study start); uncontrolled
             hypertension; or uncontrolled arrhythmias

          -  Is receiving other concomitant anticancer treatment

          -  Has received high dose chemotherapy followed by autologous stem cell transplantation
             less than 90 days prior to first dose of study treatment

          -  Is receiving concomitant therapy with strong CYP3A4 or CYP2A6 inhibitors or inducers

          -  Is pregnant or breast-feeding

          -  Participation in a clinical trial involving an investigational drug within 30 days of
             study start

          -  Known additional malignancy that is progressing or requires active treatment

          -  Has been previously treated with a Bromodomain and Extra-terminal (BET) inhibitor

          -  Has acute promyelocytic leukemia, clinically uncontrolled disseminated intravascular
             coagulation, or peripheral cytopenia

          -  Has chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the
             control of GVHD

          -  Has uncontrolled disease-related metabolic disorder

          -  Unable to swallow oral medications, or has gastrointestinal condition deemed to
             jeopardize intestinal absorption.