A Study of JNJ-26866138 (Bortezomib) in Untreated Multiple Myeloma Patients Who Are Not Candidates for Hematopoietic Stem Cell Transplant (HSCT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier:
NCT00985959
First received: September 18, 2009
Last updated: October 31, 2013
Last verified: October 2013
  Purpose

The purpose of the study in Phase I is to select the recommended dose of bortezomib in combination with melphalan and prednisolone in Japanese participants. In Phase II, to assess the effectiveness and safety of the recommended dose of bortezomib (selected in the phase I portion).


Condition Intervention Phase
Multiple Myeloma
Drug: JNJ-26866138 0.7 mg/m2
Drug: JNJ-26866138 1.0 mg/m2
Drug: JNJ-26866138 1.3 mg/m2
Drug: Melphalan
Drug: Prednisolone
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Study of JNJ-26866138 (Bortezomib) in Untreated Multiple Myeloma Patients Who Are Not Candidates for Hematopoietic Stem Cell Transplant (HSCT)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicity During the Phase I (Cycle 1) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during 6 weeks of treatment Cycle 1

  • Number of Participants With Overall Response (Complete Response [CR] + Partial Response [PR]) - Phase I and II [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
    Response is evaluated as per the criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation (Blade et al. 1998). CR: disappearance of the original monoclonal protein from the blood and urine and <5% plasma cells in the bone marrow on at least 2 determinations for a minimum of 6 weeks; no increase in the size or number of lytic bone lesions; disappearance of soft tissue plasmacytomas for at least 6 weeks. PR: ≥50% reduction in the level of serum monoclonal protein for at least 2 determinations 6 weeks apart; If present, reduction in 24-hour urinary light chain excretion by either ≥90% or to <200 mg for at least 2 determinations 6 weeks apart; ≥50% reduction in the size of soft tissue plasmacytomas for at least 6 weeks; no increase in size or number of lytic bone lesions


Secondary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 Alone) - Phase I [ Time Frame: Day 25 of Cycle 1 ] [ Designated as safety issue: No ]
    Cmax of bortezomib following intravenous administration of JNJ-26866138 at dose of 0.7, 1.0, and 1.3 mg/m2 on Cycle 1/Day 25 (JNJ-26866138 alone)

  • Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 in Combination With Melphalan and Prednisolone) - Phase I [ Time Frame: Day 4 of Cycle 2 ] [ Designated as safety issue: No ]
    Cmax of bortezomib following intravenous administration of JNJ-26866138 at dose of 0.7, 1.0, and 1.3 mg/m2 on Cycle 2/Day 4 (combination with melphalan and prednisolone)

  • Maximum Observed Plasma Concentration (Cmax) of Melphalan - Phase I [ Time Frame: Day 4 of Cycle 2 ] [ Designated as safety issue: No ]
    Cmax of melphalan at dose of 9 mg/m2 on Cycle 2/Day 4

  • Maximum Observed Plasma Concentration (Cmax) of Prednisolone - Phase I [ Time Frame: Day 4 of Cycle 2 ] [ Designated as safety issue: No ]
    Cmax of Prednisolone at dose of 60 mg/m2 on Cycle 2/Day 4

  • Median Time to First Response - Phase II [ Time Frame: up to 54 weeks ] [ Designated as safety issue: No ]
    Time to first response is the duartion of time required to achieve first response to treatment


Enrollment: 101
Study Start Date: July 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: JNJ-26866138 0.7 mg/m2
JNJ-26866138 0.7 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles.
Drug: JNJ-26866138 0.7 mg/m2
JNJ-26866138 0.7 mg/m2 will be administered intravenously on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles.
Other Name: bortezomib
Drug: Melphalan
Melphalan 9 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Drug: Prednisolone
Prednisolone 60 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Experimental: Phase I: JNJ-26866138 1.0 mg/m2
JNJ-26866138 1.0 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles
Drug: JNJ-26866138 1.0 mg/m2
JNJ-26866138 1.0 mg/m2 will be administered intravenously on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles
Other Name: bortezomib
Drug: Melphalan
Melphalan 9 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Drug: Prednisolone
Prednisolone 60 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Experimental: Phase I: JNJ-26866138 1.3 mg/m2
JNJ-26866138 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 4 cycles
Drug: JNJ-26866138 1.3 mg/m2
Phase I: JNJ-26866138 1.3 mg/m2 will be administered intravenously on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Phase II: JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5 to 9 cycles.
Other Name: bortezomib
Drug: Melphalan
Melphalan 9 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Drug: Prednisolone
Prednisolone 60 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Experimental: Phase II: JNJ-26866138 1.3 mg/m2
JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5-9 cycles. Melphalan 9 mg/m2 and Prednisolone 60 mg/m2 on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Drug: JNJ-26866138 1.3 mg/m2
Phase I: JNJ-26866138 1.3 mg/m2 will be administered intravenously on Days 1, 4, 8, 11, 22, 25, 29 and 32 of 6-week cycle up to 4 cycles. Phase II: JNJ-26866138 1.3 mg/m2 on Days 1, 8, 22 and 29 of 6-week cycle for 5 to 9 cycles.
Other Name: bortezomib
Drug: Melphalan
Melphalan 9 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles
Drug: Prednisolone
Prednisolone 60 mg/m2 will be taken orally (by mouth) on Days 1, 2, 3 and 4 of 6-week cycle up to 9 cycles

Detailed Description:

This is an open-label (both physician and participant know the intervention), non-randomized (participants are not assigned by chance), multi-center study in untreated multiple myeloma participants who were not candidates for hematopoietic stem cell transplant. This study consists of two parts: Phase I and Phase II. In Phase I, a total of 18 participants will be enrolled ie, 6 patients per dose level (0.7, 1.0 and 1.3 mg/m2) to determine the recommended dose of bortezomib. In Phase II, additional 83 participants will be enrolled. Safety evaluations will include assessment of adverse events, clinical laboratory test, specifically hematological toxicities.

  Eligibility

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

Inclusion Criteria:

  • Participants diagnosed with symptomatic or nonsecretory multiple myeloma
  • Participants who have not received chemotherapy and are not hematopoietic stem cell transplantation candidates
  • Participants with a measurable lesion
  • Life expectancy greater than or equal to 3 months

Exclusion Criteria:

  • Previously received treatment for Multiple Myeloma
  • Greater than or equal to Grade 2 peripheral neuropathy or neuropathic pain
  • Myocardial infarction within 6 months prior to enrollment or uncontrolled angina, severe uncontrolled ventricular arrhythmias, or clinically significant conduction system abnormalities
  • Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection
  • Active prior malignancy diagnosed within the last 5 years
  • Female participant who is pregnant or breast-feeding
  • Participant is enrolled in another clinical research study and/or is receiving an investigational agent
  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: NCT00985959

Locations
Japan
Fukuoka, Japan
Hiroshima N/A, Japan
Hitachi, Japan
Isehara, Japan
Kamogawa, Japan
Kanazawa, Japan
Kawagoe, Japan
Kobe, Japan
Koto-Ku, Japan
Kumamoto, Japan
Kurashiki, Japan
Kurume, Japan
Kyoto, Japan
Nagasaki, Japan
Nagoya, Japan
Narita, Japan
Niigata, Japan
Okayama, Japan
Osaka-Sayama, Japan
Sapporo, Japan
Shibukawa, Japan
Suita, Japan
Tokushima N/A, Japan
Tokyo, Japan
Toyama-City, Japan
Toyohashi, Japan
Utsunomiya, Japan
Yokohama, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K., Japan Clinical Trial Janssen Pharmaceutical K.K.
  More Information

No publications provided

Responsible Party: Janssen Pharmaceutical K.K.
ClinicalTrials.gov Identifier: NCT00985959     History of Changes
Other Study ID Numbers: CR014776, JNJ-26866138-JPN-MM-102
Study First Received: September 18, 2009
Results First Received: May 30, 2013
Last Updated: October 31, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Janssen Pharmaceutical K.K.:
Multiple myeloma
Hematopoietic stem cell transplant
HSCT
Melphalan
Prednisolone
Bortezomib
JNJ-26866138

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
Bortezomib
Prednisolone
Methylprednisolone Hemisuccinate
Melphalan
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 22, 2014