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

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00985959
• Other study ID #: CR014776
• Secondary ID: JNJ-26866138-JPN
• Status: Completed
• Phase: Phase 1
• First received: September 18, 2009
• Last updated: October 31, 2013
• Start date: July 2008
• Est. completion date: June 2010

Study information

• Verified date: October 2013
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.
• 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
• 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.
• 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
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicity During the Phase I (Cycle 1)	Dose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during 6 weeks of treatment Cycle 1	6 weeks	Yes
Primary	Number of Participants With Overall Response (Complete Response [CR] + Partial Response [PR]) - Phase I and II	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	54 weeks	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 Alone) - Phase I	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)	Day 25 of Cycle 1	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Bortezomib (JNJ-26866138 in Combination With Melphalan and Prednisolone) - Phase I	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)	Day 4 of Cycle 2	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Melphalan - Phase I	Cmax of melphalan at dose of 9 mg/m2 on Cycle 2/Day 4	Day 4 of Cycle 2	No
Secondary	Maximum Observed Plasma Concentration (Cmax) of Prednisolone - Phase I	Cmax of Prednisolone at dose of 60 mg/m2 on Cycle 2/Day 4	Day 4 of Cycle 2	No
Secondary	Median Time to First Response - Phase II	Time to first response is the duartion of time required to achieve first response to treatment	up to 54 weeks	No