Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma - Clinical Trial for Multiple Myeloma | NCT02739594

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Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

Germany

Study Type

Interventional

Intervention

Ibandronate

Zoledronate

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Confirmed multiple myeloma, Stage II-III as per Salmon and Durie (1975)
Indication for biphosphonate therapy

Exclusion Criteria:

Previous therapy with ibandronate or zoledronate within the past 12 months
Renal insufficiency with serum creatinine >3.0 mg/dL or >265 micromoles per liter (µmol/L) or CrCl <30 mL/min
Hypersensitivity to ibandronate, zoledronate, or other biphosphonates
Presence of secondary malignomas, apart from basaliomas and cervical carcinoma in situ
Severe accompanying illness with organ impairment
Osteonecrosis of the jaw at the start of the study
Life expectancy ≤12 months

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ibandronate

Zoledronate

Arm Description

Participants with multiple myeloma will be randomized to receive ibandronate every 4 weeks for a planned duration of 92 weeks.

Participants with multiple myeloma will be randomized to receive zoledronate every 4 weeks for a planned duration of 92 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30 percent (%) from Baseline or an absolute value less than or equal to (≤) 30 milliliters per minute (mL/min) at Week 44. The last available value on/before Week 44 was used in the calculation. The percentage of participants with deterioration in renal function at Week 44 was reported.

Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30% from Baseline or an absolute value ≤30 mL/min at Week 92. The last available value on/before Week 92 was used in the calculation. The percentage of participants with deterioration in renal function at Week 92 was reported.

Secondary Outcome Measures

Percentage of Participants With Skeletal-Related Events (SREs)

SREs were defined according to the Bondronat Summary of Product Characteristics (SmPC) to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The percentage of participants with at least 1 SRE during the study was reported.

Time to First SRE

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. Time to first SRE was defined as the time from first dose of study drug to the time of SRE during the study. The median time to first SRE was estimated by Kaplan-Meier analysis and expressed in days.

Number of SREs for Each Participant

SREs were defined according to the Bondronat SmPC to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The number of SREs was averaged across all participants, including those participants who did not experience SREs during the study.

Percentage of Participants With Osteonecrosis of Jaw

The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported.

Number of Events of Osteonecrosis of Jaw for Each Participant

The number of events of osteonecrosis of jaw was averaged across all participants, including those participants who did not experience the event during the study.

Percentage of Participants With Zoledronate Dose Reduction

The percentage of participants with at least 1 zoledronate dose reduction during the study was reported.

Number of Zoledronate Dose Reductions for Each Participant

The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study.

Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG)

The percent change in B-NAG was calculated as [Week 44 or 92 B-NAG minus Baseline B-NAG] divided by Baseline B-NAG, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Percent Change From Baseline in Alpha (A) 1-Microglobulin

The percent change in A1-microglobulin was calculated as [Week 44 or 92 A1-microglobulin minus Baseline A1-microglobulin] divided by Baseline A1-microglobulin, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Percent Change From Baseline in Gamma-Glutamyltransferase (GGT)

The percent change in GGT was calculated as [Week 44 or 92 GGT minus Baseline GGT] divided by Baseline GGT, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline

Elevation in SCr was defined as an increase greater than (>) 0.5 milligrams per deciliter (mg/dL) for participants with Baseline SCr less than (<) 1.4 mg/dL, or an increase >1.0 mg/dL for participants with Baseline SCr greater than or equal to (≥) 1.4 mg/dL. For the Week 44 analysis, the last available value on/before Week 44 was used. For the Week 92 analysis, the last available value on/before Week 92 was used. The percentage of participants with elevation of SCr at Weeks 44 and 92 was reported.

Percent Change From Baseline in CrCl

CrCl was calculated from blood samples using the Cockcroft-Gault formula, and was also measured by urinalysis. The percent change in CrCl was calculated as [Week 44 or 92 CrCl minus Baseline CrCl] divided by Baseline CrCl, multiplied by 100. For the Week 44 analysis, the last available value on/before Week 44 was used in the calculation. For the Week 92 analysis, the last available value on/before Week 92 was used in the calculation.

Full Information

NCT ID

NCT02739594

First Posted

April 12, 2016

Last Updated

June 9, 2016

Sponsor

Hoffmann-La Roche

Collaborators

Roche Pharma AG

1. Study Identification

Unique Protocol Identification Number

NCT02739594

Brief Title

Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma

Acronym

COMPARE

Official Title

COMPARE: Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Patients With Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

June 2016

Overall Recruitment Status

Terminated

Why Stopped

Slow recruitment

Study Start Date

February 2006 (undefined)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

Collaborators

Roche Pharma AG

4. Oversight

5. Study Description

Brief Summary

This multicenter, open-label trial will randomize participants with multiple myeloma to a regimen of ibandronate or zoledronate in order to compare the incidence of nephrotoxicity, measured as creatinine clearance (CrCl) reduction greater than (>) 30 percent (%) or an absolute value of 30 milliliters per minute (mL/min) or lower.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

89 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ibandronate

Arm Type

Experimental

Arm Description

Participants with multiple myeloma will be randomized to receive ibandronate every 4 weeks for a planned duration of 92 weeks.

Arm Title

Zoledronate

Arm Type

Active Comparator

Arm Description

Participants with multiple myeloma will be randomized to receive zoledronate every 4 weeks for a planned duration of 92 weeks.

Intervention Type

Drug

Intervention Name(s)

Ibandronate

Other Intervention Name(s)

Bondronat

Intervention Description

Ibandronate will be administered via 15-minute intravenous (IV) infusion as 6 milligrams (mg) every 4 weeks for 92 weeks.

Intervention Type

Drug

Intervention Name(s)

Zoledronate

Intervention Description

Zoledronate will be administered via 15-minute IV infusion as 4 mg every 4 weeks for 92 weeks.

Primary Outcome Measure Information:

Title

Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44

Description

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30 percent (%) from Baseline or an absolute value less than or equal to (≤) 30 milliliters per minute (mL/min) at Week 44. The last available value on/before Week 44 was used in the calculation. The percentage of participants with deterioration in renal function at Week 44 was reported.

Time Frame

Baseline, Week 44

Title

Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92

Description

CrCl was calculated from blood samples using the Cockcroft-Gault formula. Relevant deterioration in renal function was defined as CrCl reduction of 30% from Baseline or an absolute value ≤30 mL/min at Week 92. The last available value on/before Week 92 was used in the calculation. The percentage of participants with deterioration in renal function at Week 92 was reported.

Time Frame

Baseline, Week 92

Secondary Outcome Measure Information:

Title

Percentage of Participants With Skeletal-Related Events (SREs)

Description

SREs were defined according to the Bondronat Summary of Product Characteristics (SmPC) to include radiotherapy to bone for treatment of fractures/impending fractures, surgery to bone for treatment of fractures, vertebral fractures, and non-vertebral fractures. The percentage of participants with at least 1 SRE during the study was reported.

Time Frame