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A Phase I, Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015 in Haematological Malignancies

Phase 1
18 Years
Open (Enrolling)
Acute Leukemia, Other Hematological Malignacies

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Trial Information

A Phase I, Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015 in Haematological Malignancies

Inclusion Criteria:

- Signed informed consent prior to beginning protocol specific procedures. Patients
registered for this trial must be treated and followed at the participating centers.

- Histologically or cytologically proven hematological malignancy, or confirmed
multiple myeloma using standard diagnosis criteria. For the dose finding part, any
refractory/relapsing hematological malignancy will be accepted. For the expansion
cohorts, only patients with selected hematological malignancies will be enrolled :
acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), DLBCL and MM)
and/or other diseases, as decided by the SMC after closure of the dose finding part.

- Patient having failed all standard therapies or for whom standard treatment are

- For acute leukemia: patients < 60 years old in second relapse or relapsing > 90
days after allogeneic stem cell transplantation; patients> 60 years old in first
relapse with a disease-free interval (DFI) < 12 months; Patients with
Philadelphia chromosome positive (Ph+) and/or bcr-abl+ B-cell ALL must have
received at least two lines of therapy, including 2 bcr-abl tyrosine-kinase (TK)
inhibitors (among imatinib, nilotinib and dasatinib), or only one line including
one TK inhibitor, if the relapse/refractoriness is associated with the detection
of a resistance mutation to these inhibitors.

- For MM: patients adequately exposed to at least one alkylating agent, one
corticosteroid, one immunomodulatory drug (IMiD) and bortezomib,

- For lymphomas : Patients having failed 2 standard lines of therapy (at least one
containing an anti-CD20 antibody if B-cell lymphoma), or for whom such treatment
is contra-indicated.

- Patients with evaluable disease

- AL patients must have > 5% bone marrow blasts at study entry, without
alternative causality (e.g. bone marrow regeneration)

- Lymphoma patients must have at least one non-irradiated tumor mass > 15 mm (long
axis of lymph node) or > 10 mm (short axis of lymph node or extranodal lesions)
on spiral CT-scan.

- Patients with MM must have at least one of the following: serum monoclonal
component > 1g/dL (IgG), or > 0.5g/dL (IgA), or Bence-Jones (BJ) proteinuria >
200mg/24h, or measurable plasmacytoma (not previously irradiated).

- Patients > 18 years old.

- Life expectancy of at least 3 months

- ECOG performance status of 0 to 2

- Off previous therapy for at least 3 weeks, or 5 half-lives of previously administered
drug, whichever is longer, prior to first study treatment administration, except
hydroxyurea given to control hyperleukocytosis that should be stopped 48 hours prior
to start study medication.

- Recovery from the non-hematological toxic effects of prior treatment to grade < 1, or
baseline value, according to NCI-CTC classification, except alopecia.

- Bone marrow function:

- For patients with acute leukemia: No limitation

- For patients with other hematological malignancies: Neutrophils > 1.0 x 10e9 /L
and platelets > 50 x 10e9 /L (without transfusion),

- Calculated creatinine clearance > 60 mL/min (Cockroft & Gault formula, or MDRD
formula for patients aged > 65 years). For patients with MM, a creatinine clearance >
30mL/min is accepted).

- Adequate LFTs: Total bilirubin < the institutional upper normal limits (UNL);
ALAT/ASAT and AP < 3 x UNL (or < 5 x UNL in case of liver involvement).

- Serum albumin > 28g/L

- Complete baseline disease assessment workup prior to first study treatment

Exclusion Criteria:

- History of prior malignancy other than those previously treated with a curative
intent more than 5 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 disease-free interval.

- Pregnant or lactating women or women of childbearing potential not using adequate
contraception. Male patients not using adequate contraception.

- Patients with peripheral cytopenias (i.e. auto-immune hemolytic anemia or

- Patients with acute promyelocytic leukemia or with uncontrolled disseminated
intravascular coagulation

- MM patients with POEMS syndrome or plasma cell leukemia.

- Patient with 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..)

- Uncontrolled disease-related metabolic disorder (e.g. hypercalcemia)

- Patients unable to swallow oral medications, or patients with gastrointestinal
condition (e.g. malabsorption, resection…) deemed to jeopardize intestinal

- Other serious illness or medical conditions, which, in the investigator's opinion
could hamper understanding of the study by the patient, patient's compliance to study
treatment, patient'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 from 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 HIV positivity

- Concurrent treatment with other experimental therapies or participation in another
clinical trial within 21 days prior to first study treatment administration, or 5
half-lives of previously administered drugs, whichever is longer.

- Concurrent treatment or within 21 days prior to first study treatment administration
with any other anticancer therapy, except hydroxyurea to reduced hyperleukocytosis.

- Concomitant treatment with corticosteroids except if chronic treatment with
corticosteroids < 20 mg of methylprednisolone daily or equivalent.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose Limiting Toxicity for determination of the Recommended Dose

Outcome Time Frame:

21 first days of treatment

Safety Issue:



France: ANSM - Agence Nationale de Sécurité du Médicament et des produits de santé

Study ID:




Start Date:

December 2012

Completion Date:

July 2014

Related Keywords:

  • Acute Leukemia
  • Other Hematological Malignacies
  • Leukemia
  • Hematologic Neoplasms