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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01464112
First received: August 30, 2011
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Multiple Myeloma
Drug: JNJ-2641585 / VELCADE / Dexamethasone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Determine the dose-limiting toxicity and set the MTD for the combination of JNJ-26481585 and VELCADE-dexamethasone [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
    Based on the safety analysis of all cohorts using the patients-treated population


Secondary Outcome Measures:
  • Adverse events [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
    As a measure of safety

  • Clinical laboratory tests [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
    As a measure of safety

  • Overall response rate [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetics evaluations for JNJ-26481585 [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
    Cmax, Area Under Curve, Tmax

  • Profile of pharmacokinetics evaluations for VELCADE [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
    Cmax, Area Under Curve, Tmax

  • Bone cell morphology [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Pulse [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Heart rate [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Body temperature [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Height [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Weight [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]
  • Body surface area [ Time Frame: Maximum of 18 months ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2011
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

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

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
  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: NCT01464112

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

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01464112     History of Changes
Other Study ID Numbers: CR018661, 26481585MMY1001, 2011-001001-27
Study First Received: August 30, 2011
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on November 23, 2014