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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I: JNJ-26866138 0.7 mg/m2<br>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<br>* 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.<br>* Other names: bortezomib;Drug: Melphalan<br>* 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<br>Drug: Prednisolone<br>* 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<br>|
| Experimental: Phase I: JNJ-26866138 1.0 mg/m2<br>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<br>* 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<br>* Other names: bortezomib;Drug: Melphalan<br>* 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<br>Drug: Prednisolone<br>* 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<br>|
| Experimental: Phase I: JNJ-26866138 1.3 mg/m2<br>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<br>* 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.<br>* Other names: bortezomib;Drug: Melphalan<br>* 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<br>Drug: Prednisolone<br>* 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<br>|
| Experimental: Phase II: JNJ-26866138 1.3 mg/m2<br>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<br>* 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.<br>* Other names: bortezomib;Drug: Melphalan<br>* 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<br>Drug: Prednisolone<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, Hematopoietic stem cell transplant, HSCT, Melphalan, Prednisolone, Bortezomib, JNJ-26866138