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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

Phase 1
18 Years
Open (Enrolling)
Multiple Myeloma

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Trial Information

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

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toxicity will be withdrawn from treatment.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.

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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the dose-limiting toxicity and set the MTD for the combination of JNJ-26481585 and VELCADE-dexamethasone

Outcome Description:

Based on the safety analysis of all cohorts using the patients-treated population

Outcome Time Frame:

Maximum of 18 months

Safety Issue:


Principal Investigator

Janssen Research & Development, LLC & Development, L.L.C. Clinical Trial

Investigator Role:

Study Director

Investigator Affiliation:

Janssen Research & Development, LLC


United States: Food and Drug Administration

Study ID:




Start Date:

September 2011

Completion Date:

March 2013

Related Keywords:

  • Multiple Myeloma
  • Multiple myeloma that has relapsed or is progressive following prior therapy
  • Relapsed Multiple Myeloma
  • JNJ 26481585
  • Bortezomib
  • Dexamethasone
  • Multiple Myeloma
  • Neoplasms, Plasma Cell