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

This study has been completed.
Information provided by (Responsible Party):
Oncoethix GmbH Identifier:
First received: October 22, 2012
Last updated: February 23, 2017
Last verified: February 2017
The primary purpose of this study is to determine the recommended dose (RD) of OTX015/MK-8628 for further phase II studies, in participants with acute leukemias (acute myeloid leukemia [AML; de novo and secondary to a myelodysplastic syndrome] or acute lymphoblastic leukemia [ALL]) or hematologic malignancies (diffuse large B cell lymphoma [DLBCL] or multiple myeloma [MM]).

Condition Intervention Phase
Acute Myeloid Leukemia
Diffuse Large B-cell Lymphoma
Acute Lymphoblastic Leukemia
Multiple Myeloma
Drug: OTX015/MK-8628
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I, Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/MK-8628 in Hematologic Malignancies

Resource links provided by NLM:

Further study details as provided by Oncoethix GmbH:

Primary Outcome Measures:
  • Number of Participants with One or More Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 21 days ]

Enrollment: 141
Study Start Date: December 2012
Study Completion Date: January 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acute Leukemia Participants
Participants with AML or ALL receive OTX015/MK-8628 at a starting dose of 10 mg, orally (PO) once per day (QD) continuously for 21 days per cycle.
Drug: OTX015/MK-8628
OTX015/MK-8628 10 mg, 20 mg or 40 mg capsules
Experimental: Hematologic Malignancy Participants
Participants with DLBCL or MM receive OTX015/MK-8628 at a starting dose of 10 mg, PO QD continuously for 21 days per cycle.
Drug: OTX015/MK-8628
OTX015/MK-8628 10 mg, 20 mg or 40 mg capsules


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT01713582

Sponsors and Collaborators
Oncoethix GmbH
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Oncoethix GmbH Identifier: NCT01713582     History of Changes
Obsolete Identifiers: NCT02542358
Other Study ID Numbers: 8628-001
OTX015_104 ( Other Identifier: OncoEthix Protocol Number )
2012-003380-22 ( EudraCT Number )
Study First Received: October 22, 2012
Last Updated: February 23, 2017

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Multiple Myeloma
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Leukemia, Myeloid
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoma processed this record on March 29, 2017