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.