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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by Oncoethix GmbH
Information provided by (Responsible Party):
Oncoethix GmbH
ClinicalTrials.gov Identifier:
First received: October 22, 2012
Last updated: September 21, 2015
Last verified: September 2015

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 myeloid leukemia (AML; AML de novo and AML secondary to a myelodysplastic syndrome) and in participants with diffuse large B cell lymphoma (DLBCL).

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: December 2012
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AML Participants
Participants with AML receive OTX015/MK-8628 20 mg or 30 mg, orally (PO) twice per day (BID) continuously for 21 days per cycle.
Drug: OTX015/MK-8628
OTX015/MK-8628 10 mg or 20 mg capsules
Experimental: DLBCL Participants
Participants with DLBCL receive OTX015/MK-8628 20 mg or 30 mg, PO BID continuously for 21 days per cycle.
Drug: OTX015/MK-8628
OTX015/MK-8628 10 mg or 20 mg capsules


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically or cytologically proven AML or DLBCL using standard diagnosis criteria. AML includes AML de novo and AML 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 treatment are contra-indicated:

    • AML 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 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.
  • For participants with evaluable disease:

    • AML participants must have >5% bone marrow blasts at study entry, without alternative causality (e.g. bone marrow regeneration)
    • DLBCL participants must have ≥1non-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.
  • Life expectancy ≥3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Off previous therapy ≥2 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 2 weeks prior to first study drug administration.
  • Concurrent treatment or treatment within 2 weeks 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01713582

Contact: Susan Perez, MD 1-732-594-1414 susan.perez@merck.com
Contact: Abraham Leung, MD 1-732-594-5161 abraham.leung@merck.com

Canada, Quebec
Merck Canada Recruiting
Kirkland, Quebec, Canada, H9H 3L1
Contact: Medical Information Centre Centre de l'information medicale de Merck Canada    514-428-8600 / 1-800-567-2594      
MSD France Recruiting
Paris, France
Contact: Dominique Blazy    33 147548990      
MSD International GmbH Recruiting
Lucerne 6, Switzerland
Contact: Erik Mossdorf    41 58 618 33 79      
United Kingdom
Merck Sharp & Dohme Ltd. Recruiting
Hoddesdon, United Kingdom
Contact: Mark Toms    +44 (0) 1992 452475      
Sponsors and Collaborators
Oncoethix GmbH
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Oncoethix GmbH
ClinicalTrials.gov Identifier: NCT01713582     History of Changes
Obsolete Identifiers: NCT02542358
Other Study ID Numbers: 8628-001, OTX015_104, 2012-003380-22
Study First Received: October 22, 2012
Last Updated: September 21, 2015
Health Authority: France: ANSM - Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: ISS - Istituto Superiore di Sanita
Switzerland: Swissmedic

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Leukemia, Myeloid
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 07, 2015