A Dose Escalation Study of the Histone Deacetylase Inhibitor (HDACi) JNJ 26481585 in Combination With VELCADE (Bortezomib) and Dexamethasone for Patients With Relapsed Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01464112
Recruitment Status : Completed
First Posted : November 3, 2011
Last Update Posted : January 2, 2017
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability and to establish the maximum tolerated dose of JNJ-26481585 combined with VELCADE and dexamethasone.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: JNJ-2641585 / VELCADE / Dexamethasone Phase 1

Detailed Description:
This is an open-label (patient and study personnel will know what treatment is being administered), multicenter, dose escalation study. Increasing doses of JNJ-26481585 will be explored in combination with the standard VELCADE/dexamethasone dose. After the maximum tolerated dose (MTD) is determined, up to 24 patients will be entered in a treatment group to receive the MTD (and if deemed necessary a lower dose level) to further assess the safety and activity of this combination. There will be 3 phases in the study: a Screening Phase (from signing of informed consent until immediately before dosing), an open-label Treatment Phase (from the first dose of JNJ-26481585 and VELCADE-dexamethasone until the End of Treatment Visit), and a Posttreatment/Follow-up Phase. Patients who achieve a positive response to treatment at the end of Cycle 1 will continue to receive JNJ-26481585 and VELCADE-dexamethasone for a maximum of 11 cycles (eight 3-week treatment cycles, followed by three 5-week treatment cycles). Patients with progressive disease (PD) or unacceptable toxicity will be withdrawn from treatment. In the Follow-Up Phase, patients whose disease has not progressed or who discontinued treatment for reasons other than PD will be assessed approximately every 6 weeks until PD is recorded or until the start of subsequent therapy. The study will end when all patients have been assessed with PD, or 12 months after the last patient is enrolled, whichever is earlier. Patient safety will be monitored. Drug A, JNJ-26481585, will be taken orally on Days 1, 3, and 5 of each week at doses starting at 6 mg and escalating to 12 mg. Drug B, VELCADE, will be given by subcutaneous injection (under the skin) at a dose of 1.3 mg/m2 on Days 1, 4, 8, and 11 of each 21-day cycle (Cycles 1 to 8) and on Days 1, 8, 15, and 22 of each 35-day cycle (Cycles 9-11). Drug C, dexamethasone, will be taken orally on the day of and after VELCADE at a dose of 20 mg. Dosing may be adjusted, based on tolerability.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of the Histone Deacetylase Inhibitor (HDACi) JNJ-26481585 in Combination With VELCADE (Bortezomib) and Dexamethasone for Subjects With Relapsed Multiple Myeloma
Study Start Date : September 2011
Actual Primary Completion Date : November 2013
Actual Study Completion Date : November 2013

Arm Intervention/treatment
Experimental: 001 Drug: JNJ-2641585 / VELCADE / Dexamethasone
JNJ-26481585: type=range, unit=mg, number=6 to 12, form=capsules, route=oral use, on Days 1, 3, and 5 of each week. VELCADE: type=exact, unit=mg/m2, number=1.3, form=powder for solution for injection, route=subcutaneous use, on Days 1, 4, 8, and 11 of each 21-day cycle (Cycles 1 to 8) and on Days 1, 8, 15, and 22 of each 35-day cycle (Cycles 9-11). Dexamethasone: type=exact, unit=mg, number=20, form=tablets, route=oral use, on the day of and after VELCADE.

Primary Outcome Measures :
  1. Determine the dose-limiting toxicity and set the MTD for the combination of JNJ-26481585 and VELCADE-dexamethasone [ Time Frame: Maximum of 18 months ]
    Based on the safety analysis of all cohorts using the patients-treated population

Secondary Outcome Measures :
  1. Adverse events [ Time Frame: Maximum of 18 months ]
    As a measure of safety

  2. Clinical laboratory tests [ Time Frame: Maximum of 18 months ]
    As a measure of safety

  3. Overall response rate [ Time Frame: Maximum of 18 months ]
  4. Duration of response [ Time Frame: Maximum of 18 months ]
  5. Profile of pharmacokinetics evaluations for JNJ-26481585 [ Time Frame: Maximum of 18 months ]
    Cmax, Area Under Curve, Tmax

  6. Profile of pharmacokinetics evaluations for VELCADE [ Time Frame: Maximum of 18 months ]
    Cmax, Area Under Curve, Tmax

  7. Bone cell morphology [ Time Frame: Maximum of 18 months ]
  8. Pulse [ Time Frame: Maximum of 18 months ]
  9. Heart rate [ Time Frame: Maximum of 18 months ]
  10. Blood pressure [ Time Frame: Maximum of 18 months ]
  11. Body temperature [ Time Frame: Maximum of 18 months ]
  12. Height [ Time Frame: Maximum of 18 months ]
  13. Weight [ Time Frame: Maximum of 18 months ]
  14. Body surface area [ Time Frame: Maximum of 18 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) Performance status score 0-2
  • Measurable or secretory multiple myeloma
  • Relapse or progression of myeloma following prior systemic antineoplastic therapy
  • Pretreatment clinical laboratory values meeting protocol-specified criteria
  • Left ventricular ejection fraction rate within normal limits

Exclusion Criteria:

  • Peripheral neuropathy or neuralgia >=2, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0
  • Diagnosis of primary amyloidosis, plasma cell leukemia, or other similar conditions
  • Diagnosis of Waldenstrom macroglobulinemia with protocol-specified immunoglobulin levels
  • Prior histone-deacetylase inhibitor therapy - More than 3 prior lines of therapy
  • Cardiac risk factors: unstable angina or myocardial infarction within the preceding 12 months, congestive heart failure (New York Heart Association Class II-IV), known presence of dilated, hypertrophic, or restrictive cardiomyopathy
  • Any other cardiac abnormality that, in the opinion of the investigator, medical monitor, or consultant cardiologist, may place the patient at an unacceptably increased risk with study drug
  • History of any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, atrial fibrillation, cardiac arrest, Mobitz II second degree heart block, or third degree heart block - QTc at Screening > 450 ms in males / > 470 ms in females
  • Family history of short QT syndrome, long QT syndrome
  • Obligate use of a cardiac pacemaker - Use of medications that may cause Torsades de Pointes

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01464112

Lille Cedex, France
Nantes, France
Tours, France
Sponsors and Collaborators
Janssen Research & Development, LLC
Study Director: Janssen Research & Development, LLC & Development, L.L.C. Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC Identifier: NCT01464112     History of Changes
Other Study ID Numbers: CR018661
26481585MMY1001 ( Other Identifier: Janssen Research & Development, LLC )
2011-001001-27 ( EudraCT Number )
First Posted: November 3, 2011    Key Record Dates
Last Update Posted: January 2, 2017
Last Verified: December 2016

Keywords provided by Janssen Research & Development, LLC:
Multiple myeloma that has relapsed or is progressive following prior therapy
Relapsed Multiple Myeloma
JNJ 26481585

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents