A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001)

Inclusion Criteria:

* Histologically or cytologically proven acute leukemias (AML or ALL) or hematologic malignancies (DLBCL or MM) using standard diagnosis criteria. Acute leukemia includes de novo and secondary to a pre-existing myelodysplastic syndrome, according to the World Health Organization 2008 classification. For DLBCL, an archived formaldehyde-fixed paraffin-embedded block must be available.
* Has failed all standard therapies or for whom standard treatments are contra-indicated:

  * Acute leukemia participants: \<60 years old in second relapse or relapsing after allogeneic stem cell transplantation (aSCT) regardless of number of relapses; \>60 years old in first relapse with a disease-free interval (DFI) \<12 months or further relapse; irrespective of age, in participants relapsing after aSCT, the time elapsed since aSCT should be \>90 days; participants with B-cell ALL: Philadelphia chromosome positive (Ph+) 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
  * DLBCL participants: Failed 2 standard lines of therapy (≥1 containing an anti-CD20 monoclonal antibody), or for whom such treatment is contra-indicated
  * MM participants: Adequately exposed to at least one alkylating agent, one corticosteroid, one immunomodulatory drug (IMiD) and bortezomib, or for whom such treatments are contra-indicated.
* For participants with evaluable disease:

  * Advanced leukemia participants must have \>5% bone marrow blasts at study entry, without alternative causality (e.g. bone marrow regeneration)
  * DLBCL participants must have ≥1 non-irradiated tumor mass ≥15 mm (long axis of lymph node) or ≥10 mm (short axis of lymph node or extranodal lesions) on spiral computed tomography (CT)-scan.
  * MM participants must have ≥1 of the following: serum monoclonal component \>1 g/dL (IgG), or \>0.5 g/dL (IgA), or Bence-Jones (BJ) proteinuria \>200 mg/24h, or measurable plasmacytoma (not previously irradiated).
* Life expectancy ≥3 months.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Off previous therapy ≥3 weeks prior to first study drug administration with full recovery from any previous toxicities, except 1) hydroxyurea single agent of in combination (e.g. + 6-Mercaptopurine \[6MP\]) to control hyperleukocytosis, which should be stopped for ≥48 hours, and 2) rituximab, which should be stopped for ≥3 weeks.
* Recovery from the non-hematologic toxic effects of prior treatment to grade ≤1, according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) classification, except alopecia.
* Adequate bone marrow function.
* Adequate calculated creatinine clearance.
* Adequate liver function tests.
* Complete baseline disease assessment workup prior to first study drug administration.

Exclusion Criteria:

* History of prior malignancy other than those previously treated with a curative intent \>3 years ago and without relapse (any tumor) or basal cell skin cancer, in situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps treated adequately, regardless of the DFI.
* Pregnant or lactating women or women of childbearing potential not using adequate contraception. Male participants not using adequate contraception.
* Peripheral cytopenias (i.e. auto-immune hemolytic anemia or thrombocytopenia).
* Acute promyelocytic leukemia or with clinically uncontrolled (i.e. with bleeding) disseminated intravascular coagulation (DIC).
* Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD.
* Uncontrolled leptomeningeal disease.
* Other tumor location necessitating an urgent therapeutic intervention (palliative care, surgery or radiation therapy), such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.
* Unable to swallow oral medications, or has gastrointestinal condition (e.g. malabsorption, resection) deemed to jeopardize intestinal absorption.
* Other serious illness or medical conditions, which, in the investigator's opinion could hamper understanding of the study by the participants, participant's compliance to study treatment, participant's safety or interpretation of study results. These conditions include (but are not restricted to):

  1. Congestive heart failure or angina pectoris except if medically controlled. Previous history of myocardial infarction within 1 year of study entry, uncontrolled hypertension or arrhythmias.
  2. Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
  3. Uncontrolled infection.
  4. Known human immunodeficiency virus (HIV) positivity
* Concurrent treatment with other experimental therapies or participation in another clinical trial within 30 days prior to first study drug administration.
* Concurrent treatment or treatment within 30 days prior to first study drug administration with any other anticancer therapy, except hydroxyurea (+/- 6MP) to control hyperleukocytosis.
* Concomitant treatment with corticosteroids except if chronic treatment with ≤30 mg of methylprednisolone daily or equivalent dose of other corticosteroids.