Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Multiple Myeloma (COMPARE)

• ClinicalTrials.gov Identifier: NCT02739594
• Recruitment Status: Terminated
• First Posted: April 15, 2016
• Results First Posted: July 22, 2016
• Last Update Posted: July 22, 2016
• Sponsor: Hoffmann-La Roche
• Collaborator: Roche Pharma AG
• Information provided by (Responsible Party): Hoffmann-La Roche

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.

Condition or disease	Intervention/treatment	Phase
Multiple Myeloma	Drug: Ibandronate; Drug: Zoledronate	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: COMPARE: Comparison of Ibandronate - Zoledronate Regarding Nephrotoxicity in Patients With Multiple Myeloma
• Study Start Date: February 2006
• Actual Primary Completion Date: April 2009
• Actual Study Completion Date: April 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ibandronate; Participants with multiple myeloma will be randomized to receive ibandronate every 4 weeks for a planned duration of 92 weeks.	Drug: Ibandronate; Ibandronate will be administered via 15-minute intravenous (IV) infusion as 6 milligrams (mg) every 4 weeks for 92 weeks.; Other Name: Bondronat
Active Comparator: Zoledronate; Participants with multiple myeloma will be randomized to receive zoledronate every 4 weeks for a planned duration of 92 weeks.	Drug: Zoledronate; Zoledronate will be administered via 15-minute IV infusion as 4 mg every 4 weeks for 92 weeks.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Deterioration in Renal Function According to Reduction in Creatinine Clearance (CrCl) From Baseline to Week 44 [ Time Frame: Baseline, 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.
2. Percentage of Participants With Deterioration in Renal Function According to Reduction in CrCl From Baseline to Week 92 [ Time Frame: Baseline, 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 :

1. Percentage of Participants With Skeletal-Related Events (SREs) [ Time Frame: From Baseline to end of study (up to Week 96) ]
   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.
2. Time to First SRE [ Time Frame: From Baseline to end of study (up to Week 96) ]
   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.
3. Number of SREs for Each Participant [ Time Frame: From Baseline to end of study (up to Week 96) ]
   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.
4. Percentage of Participants With Osteonecrosis of Jaw [ Time Frame: From Baseline to end of study (up to Week 96) ]
   The percentage of participants with at least 1 event of osteonecrosis of jaw during the study was reported.
5. Number of Events of Osteonecrosis of Jaw for Each Participant [ Time Frame: From Baseline to end of study (up to Week 96) ]
   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.
6. Percentage of Participants With Zoledronate Dose Reduction [ Time Frame: From Baseline to end of study (up to Week 96) ]
   The percentage of participants with at least 1 zoledronate dose reduction during the study was reported.
7. Number of Zoledronate Dose Reductions for Each Participant [ Time Frame: From Baseline to end of study (up to Week 96) ]
   The number of zoledronate dose reductions was averaged across all participants, including those participants who did not have any dose reductions during the study.
8. Percent Change From Baseline in N-Acetyl-Beta-D-Glucosaminidase (B-NAG) [ Time Frame: Baseline and Weeks 44, 92 ]
   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.
9. Percent Change From Baseline in Alpha (A) 1-Microglobulin [ Time Frame: Baseline and Weeks 44, 92 ]
   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.
10. Percent Change From Baseline in Gamma-Glutamyltransferase (GGT) [ Time Frame: Baseline and Weeks 44, 92 ]
    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.
11. Percentage of Participants With Elevation of Serum Creatinine (SCr) From Baseline [ Time Frame: Baseline and Weeks 44, 92 ]
    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.
12. Percent Change From Baseline in CrCl [ Time Frame: Baseline and Weeks 44, 92 ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Germany

Ansbach, Germany, 91522

Aschaffenburg, Germany, 63739

Augsburg, Germany, 86150

Berlin, Germany, 10437

Berlin, Germany, 10707

Berlin, Germany, 12627

Bremen, Germany, 28239

Duisburg, Germany, 47051

Duisburg, Germany, 47166

Erlangen, Germany, 91054

Essen, Germany, 45136

Esslingen, Germany, 73730

Frankfurt Am Main, Germany, 60389

Frankfurt Am Main, Germany, 65929

Greifswald, Germany, 17475

Göttingen, Germany, 37075

Güstrow, Germany, 18273

Gütersloh, Germany, 33332

Halle, Germany, 06110

Hamburg, Germany, 22081

Hamburg, Germany, 22457

Hamm, Germany, 59063

Hannover, Germany, 30171

Hannover, Germany, 30625

Herne, Germany, 44625

Hof, Germany, 95028

Jena, Germany, 07743

Karlsruhe, Germany, 76137

Kassel, Germany, 34117

Kassel, Germany, 34125

Koblenz, Germany, 56068

Krefeld, Germany, 47798

Köln, Germany, 50677

Köln, Germany, 50924

Leer, Germany, 26789

Leipzig, Germany, 04289

Ludwigshafen, Germany, 67063

Lübeck, Germany, 23562

Magedburg, Germany, 39104

Minden, Germany, 32427

Moers, Germany, 47441

Muenster, Germany, 48149

Mülheim, Germany, 45468

München, Germany, 80336

Neumünster, Germany, 24534

Offenbach, Germany, 63069

Offenburg, Germany, 77652

Oldenburg, Germany, 26121

Oldenburg, Germany, 26133

Stuttgart, Germany, 70174

Stuttgart, Germany, 70199

Tübingen, Germany, 72076

Weiden, Germany, 92637

Wiesbaden, Germany, 65191

Würzburg, Germany, 97080

Zwickau, Germany, 08058

Sponsors and Collaborators

Hoffmann-La Roche

Roche Pharma AG

Investigators

• Study Chair: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02739594
• Other Study ID Numbers: ML18508; 2005-003264-38 ( EudraCT Number )
• First Posted: April 15, 2016
• Results First Posted: July 22, 2016
• Last Update Posted: July 22, 2016
• Last Verified: June 2016

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; Ibandronic Acid; Zoledronic Acid; Bone Density Conservation Agents; Physiological Effects of Drugs