A Study of JNS002 (Doxorubicin Hydrochloride Liposome Injection) in Relapsed or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT01371227
First received: May 26, 2011
Last updated: July 3, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to evaluate tolerability of the combination therapy of JNS002 and bortezomib in Japanese bortezomib-naive patients with multiple myeloma who have ever received at least 1 line of chemotherapy.


Condition Intervention Phase
Multiple Myeloma
Drug: JNS002
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 of JNS002 (Doxorubicin HCl Liposome Injection) in Combination With Bortezomib for Japanese Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Janssen Pharmaceutical K.K.:

Primary Outcome Measures:
  • Number of patients with adverse events as a measure of safety and tolerability [ Time Frame: Up to 21 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of subjects who achieved a complete response or partial response [ Time Frame: Up to 126 days ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: April 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: JNS002
JNS002 30 mg/m2 by intravenous infusion at a rate of = 1 mg/minute on Day 4 of each 21-day cycle.
Drug: JNS002
30 mg/m2 by intravenous infusion at a rate of = 1 mg/minute on Day 4 of each 21-day cycle.

Detailed Description:

This is a non-randomized (study drug is intentionally assigned to the patient), single-arm (one group of patients receiving the same treatment), open-label (all people involved know the identity of the intervention) study to evaluate tolerability of the combination therapy of JNS002 and bortezomib in 3 to 6 patients with multiple myeloma whose disease has either progressed after at least 1 line of prior therapy or was refractory to initial treatment. Initially, 3 patients will be enrolled and the incidence of dose limiting toxicity (DLT) will be determined at the end of Cycle 1 to evaluate the study doses against the maximum tolerated dose (MTD). If the incidence is =2/3, additional 3 patients will be enrolled to define the MTD. Safety endpoints include adverse events, laboratory tests (hematology, blood biochemistry, and urinalysis), electrocardiogram (ECG), LVEF, chest X-ray, vital signs (body temperature, pulse rate, and blood pressure), and body weight. Efficacy evaluation will be performed in terms of antitumor effect, according to criteria for assessment of antitumor effect similar to the European Group for Blood and Marrow Transplantation (EBMT) criteria. Bortezomib 1.3 mg/m2 by rapid (bolus) intravenous (IV) administration will be given on Days 1, 4, 8, and 11 of each 21-day cycle. In addition, JNS002 30 mg/m2 by IV infusion will be given at a rate of = 1 mg/minute on Day 4 of every 21-day cycle after bortezomib. Treatment will continue for a total of 6 cycles of therapy (126 days).

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients confirmed diagnosis of multiple myeloma with evaluable disease parameters (1.Presence of M-protein in the serum and/or urine, 2.Increased plasma cells in the bone marrow or biopsy-proven plasmacytoma, 3.Presence of related organ tissue impairment)
  • Patients with progression of disease after an initial response (complete, partial, or minimal response based on the EBMT criteria) to at least 1 line of therapy. Progression of disease before responding to an initial line of therapy with a non-anthracycline containing regimen that included (at a minimum) an alkylating agent or high-dose corticosteroids. Rituximab alone or experimental agents alone were not to be considered a line of therapy
  • Patients with progressive disease as defined by one of the following: i) > 25% increase in M-protein, ii) Development of new or worsening lytic bone lesions, iii) Development of new or worsening plasmacytoma, iv) Development of new or worsening hypercalcemia (> 11.5 mg/dL or 2.8 mmol/L corrected) that is not attributable to any other cause
  • Patients with measurable secretory disease defined as either: i) Serum monoclonal protein > 1 g/dL, ii) Urine monoclonal (light chain) protein > 200 mg/24 hours
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. ECOG performance status score 2 due to pain associated with bone disorder is eligible.

Exclusion Criteria:

  • Patients with history of treatment with bortezomib
  • Patients with progressive disease while receiving an anthracycline-containing regimen
  • Patients with no change (NC) in disease status during initial therapy (patient must have had a response and then progression or progression while receiving initial therapy [primary refractory disease]
  • Patients with non-secretory disease (i.e., no measurable paraprotein in serum or urine
  • urine paraprotein level = 200 mg/24 hours)
  • Patients with prior treatment with doxorubicin or other anthracycline at cumulative doses greater than 240 mg/m2 (calculated using doxorubicin equivalent doses: 1 mg doxorubicin = 1 mg JNS002 = 1.8 mg epirubicin = 0.3 mg mitoxantrone = 0.25 mg idarubicin)
  • Patients with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy, according to Common Terminology Criteria for Adverse Events (CTCAE)
  • Patients with clinically significant heart disease, New York Heart Association (NYHA) Class II or higher heart failure
  • Patients with viral hepatitis or chronic liver disease
  • Patients with pulmonary fibrosis or interstitial pneumonitis
  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: NCT01371227

Locations
Japan
Nagoya, Japan
Okayama, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. Clinical Trial Janssen Pharmaceutical K.K.
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT01371227     History of Changes
Other Study ID Numbers: CR018085, JNS002-JPN-03
Study First Received: May 26, 2011
Last Updated: July 3, 2013
Health Authority: Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center

Keywords provided by Janssen Pharmaceutical K.K.:
Multiple myeloma
Relapsed or refractory multiple myeloma
JNS002
Bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Liposomal doxorubicin
Bortezomib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014