A Clinical Pharmacology and Exploratory Study of Bortezomib in Combination With Melphalan and Prednisolone in Previously Untreated Multiple Myeloma Patients

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: January 31, 2013
Last verified: January 2013
  Purpose

This is an open-label (both physician and patient know the treatment will be administered), non-randomized, multi-center study. Bortezomib will be administered in combination with melphalan and prednisolone to multiple myeloma patients up to 9 cycles. The objectives of the Phase 1 portion of this study are to assess the safety and to select the recommended dose of bortezomib in combination with melphalan and prednisolone and to assess the pharmacokinetic parameters (absorption, distribution, elimination, etc.). The objective of the Phase 2 portion is to assess the efficacy and safety of the recommended dose of bortezomib selected in the phase 1 portion.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Drug: Melphalan
Drug: Prednisolone
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 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:
  • Phase 1: Select a recommended dose of bortezomib based upon safety evaluation. Phase 2: Determine response rate of the combination of bortezomib, melphalan and prednisolone in patients with untreated multiple myeloma. [ Time Frame: After 9 cycles ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase 1: to make a preliminary evaluation of efficacy (anti-tumor effect) [ Time Frame: After 9 cycles ] [ Designated as safety issue: No ]
  • Phase 1: to assess the pharmacokinetics of bortezomib with or without a combination of melphalan and prednisolone [ Time Frame: Day 25 of cycle 1, Day 4 of cycle 2 ] [ Designated as safety issue: No ]
  • Phase 2: time to response and duration of response [ Time Frame: After 9 cycles ] [ Designated as safety issue: No ]

Enrollment: 99
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: 001
Bortezomib 0.7-1.3 mg/m2 on day 1 4 8 11 22 25 29 32 of 6-week cycle up to 4 cycles,Bortezomib 0.7-1.3 mg/m2 on day 1 8 22 29 of 6-week cycle for 5-9 cycles,Melphalan 9 mg/m2 on day 1 2 3 4 of 6-week cycle up to 9 cycles,Prednisolone 60 mg/m2 on day 1 2 3 4 of 6-week cycle up to 9 cycles
Drug: Bortezomib
0.7-1.3 mg/m2 on day 1, 4, 8, 11, 22, 25, 29, 32 of 6-week cycle up to 4 cycles
Drug: Melphalan
9 mg/m2 on day 1, 2, 3, 4 of 6-week cycle, up to 9 cycles
Drug: Prednisolone
60 mg/m2 on day 1, 2, 3, 4 of 6-week cycle, up to 9 cycles
Drug: Bortezomib
0.7-1.3 mg/m2 on day 1, 8, 22, 29 of 6-week cycle for 5-9 cycles

Detailed Description:

This is a phase 1/2, open-label (both physician and patient know the treatment will be administered), non-randomized, multi-center study in untreated multiple myeloma. This study consists of two portions, phase 1 portion and phase 2 portion. The objectives of this study is to assess the safety, to establish the recommended dose, to evaluate pharmacokinetic parameters (absorption, distribution, elimination,etc.) of bortezomib in the phase 1 portion, and to assess the efficacy and safety of the recommended dose of bortezomib in the phase 2 portion. Primary outcome measure is response rate (percentage of patients achieved a complete response or a partial response after the treatment) of the combination of bortezomib, melphalan and prednisolone in patients with untreated multiple myeloma. Administration method for bortezomib and combination drugs are as follows: Bortezomib will be administered intravenously on day 1, 4, 8, 11, 22, 25, 29 and 32 followed by a 10-day rest period of 6 weeks. With 6 weeks regarded as one cycle, treatment can be repeated for up to 4 cycles. At the 5th or later cycles, bortezomib will be administered intravenously on day 1, 8, 22, and 29 followed by a 13-day rest period of 6 weeks. With 6 weeks regarded as one cycle, treatment can be repeated for up to 9 cycles. Melphalan and prednisolone will be administered orally on day 1, 2, 3 and 4 followed by a 38-day rest period of 6 weeks. With the 6 weeks regarded as one cycle, treatment can be repeated for up to 9 cycles. Safety evaluation in this study includes adverse event reporting (all through the trial), vital signs examination and laboratory tests (Cycle 1 to 4: day 1, 4, 8, 11, 22, 25, 29, 32 and 42 of 6-week cycle, Cycle 5 to 9: day 1, 4, 8, 22, 29 and 42 of 6-week cycle). Dosage of bortezomib are 0.7, 1.0 and 1.3 mg/m2 in the phase I portion and either of the dose will be selected as recommended dose in the phase 2 portion. Bortezomib will be administered intravenously with 6-week cycle for up to 9 cycles. Melphalan 9mg/m2 and prednisolone 60mg/m2 will be administered orally with 6-week cycle for up to 9 cycles.

  Eligibility

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

Inclusion Criteria:

  • Patients diagnosed with symptomatic or nonsecretory multiple myeloma
  • Patients who have not received chemotherapy and are not hematopoietic stem cell transplantation candidates
  • Patients with a measurable lesion
  • Life expectancy >= 3 months

Exclusion Criteria:

  • Previously received treatment for Multiple Myeloma
  • >=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 subject who is pregnant or breast-feeding
  • Patient is enrolled in another clinical research study and/or is receiving an investigational agent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00985959

Locations
Japan
Bunkyo, Japan
Chuo, Japan
Fukuoka, Japan
Hiroshima N/A, Japan
Hitachi, Japan
Isehara, Japan
Kamogawa, Japan
Kanazawa, Japan
Kanazawa N/A, Japan
Kawagoe, Japan
Kobe, Japan
Koto-Ku, Japan
Kumamoto, Japan
Kurashiki, Japan
Kurume, Japan
Kyoto, Japan
Minato, Japan
Nagasaki, Japan
Nagoya, Japan
Nagoya N/A, Japan
Narita, Japan
Niigata, Japan
Niigata N/A, Japan
Okayama, Japan
Osaka-Sayama, Japan
Osaka-Sayama N/A, Japan
Sapporo, Japan
Shibukawa, Japan
Shibuya, Japan
Suita, Japan
Suita N/A, Japan
Tokushima N/A, Japan
Tokyo, Japan
Tokyo N/A, Japan
Toyama-City, Japan
Toyohashi, Japan
Toyohashi N/A, Japan
Utsunomiya, Japan
Yokohama, Japan
Sponsors and Collaborators
Janssen Pharmaceutical K.K.
Investigators
Study Director: Janssen Pharmaceutical K.K. 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
Last Updated: January 31, 2013
Health Authority: Japan: Japan Pharmaceuticals And Medical Devices Evaluation Center

Keywords provided by Janssen Pharmaceutical K.K.:
Multiple myeloma
Melphalan
Prednisolone
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
Melphalan
Bortezomib
Prednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2013