Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Various Levels of Renal Function

Multiple Myeloma Clinical Trial

Official title:

PH Ib Study of Elotuzumab in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma and Normal Renal Function, Severe Renal Impairment, or End Stage Renal Disease Requiring Dialysis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01393964
• Other study ID #: CA204-007
• Status: Active, not recruiting
• Phase: Phase 1
• First received: July 12, 2011
• Last updated: December 18, 2015
• Start date: January 2012
• Est. completion date: February 2016

Study information

• Verified date: December 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to assess the concentration of Elotuzumab in Myeloma patients with very low kidney function including patients on dialysis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: February 2016
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects with Multiple Myeloma (MM) and renal function fitting one of three categories:

1. Severe renal impairment: estimated creatinine clearance (CrCl) <30 ml/min, but not requiring dialysis

2. End-stage renal disease: requiring hemodialysis

3. Normal renal function: estimated CrCl =90 ml/min

• Documented evidence of symptomatic MM, either newly diagnosed or relapsed/refractory

• Prior Lenalidomide exposure is permitted only if the subject did not discontinue Lenalidomide due to a Grade =3 related Adverse Event (AE)

Exclusion Criteria:

• Monoclonal Gammopathy of Undetermined Significance (MGUS), Waldenstrom's macroglobulinemia, or smoldering myeloma

• Active plasma cell leukemia

• All adverse events of any prior chemotherapy, surgery, or radiotherapy not resolved

• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Acute renal failure

Study Design

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide
Capsules, Oral, 15 mg, One capsule every 48 hours through Days 1-21 (Repeat every 28 days until subject meets criteria for discontinuation of study drug
• Dexamethasone
Tablets, Oral, 28 mg weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug
• Dexamethasone
Tablets, Oral, 40 mg, weekly, on days 8, 15 & 22 (cycle 1); days 8 &22 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug
• Dexamethasone
Solution, Intravenous, 8 mg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond) Repeat every 28 days until subject meets criteria for discontinuation of study drug

Biological:
• Elotuzumab (BMS-901608; HuLuc63)
Solution, Intravenous, 10 mg/kg, weekly, on day 1 (cycle 1); days 1, 8, 15, 22 (cycles 2-3; days 1 &15 (cycle 4 and beyond), Repeat every 28 days until subject meets criteria for discontinuation of study drug

Locations

Country	Name	City	State
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	University Of Maryland	Baltimore	Maryland
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	The University Of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Investigative Clinical Research Of Indiana, Llc	Indianapolis	Indiana
United States	University Of Iowa Hospitals And Clinics	Iowa City	Iowa
United States	Tennessee Oncology, Pllc	Nashville	Tennessee
United States	Mount Sinai Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	Va Puget Sound Health Care System	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Geometric Mean Maximum Observed Serum Concentration (Cmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	The quantification of elotuzumab in human serum was performed using a validated Enzyme-linked immunoassay (ELISA). Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Cmax was measured in micrograms per milliliter (µg/mL). Pharmacokinetic (PK) parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.	Day 1 of Cycle 1 to 28 days post dose	No
Primary	Geometric Mean Area Under Serum Concentration-Time Curve From Time Zero to Time of Last Quantifiable Concentration AUC(0-T) and From Time Zero Extrapolated to Infinite Time AUC(INF) of Elotuzumab Following Cycle 1, Day 1 - Grouping by C-G CrCl Method	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD participants had 2 additional sample times: immediately prior to and immediately after dialysis. AUC was measured in µg*h/mL. PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group	Day 1 of Cycle 1 to 28 days post dose	No
Secondary	Median Time to Maximal Concentration (Tmax) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Tmax was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.	Day 1 of Cycle 1 to 28 days post dose	No
Secondary	Mean Terminal-phase Elimination Half-life (T-Half) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. T-Half was measured in hours (h). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.	Day 1 of Cycle 1 to 28 days post dose	No
Secondary	Geometric Mean Total Body Clearance (CLT) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. CLT was measured in mL per hour per kilogram body weight (mL/h/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.	Day 1 of Cycle 1 to 28 days post dose	No
Secondary	Geometric Mean Apparent Volume of Distribution (Vz) of Elotuzumab Following Cycle 1, Day 1 Dose Administration - Grouping by Cockcroft-Gault Creatinine Clearance Method	The quantification of elotuzumab in human serum was performed using validated ELISA. Cycle 1, day 1 sample times for all participants: 0 hour (h) pre-dose, end of infusion, 30 minutes (min) post end of infusion, 2 h, 4 h , and 24 h post end of infusion. Trough samples were obtained in subsequent cycles and at 30 day and 60 day follow-up visits at end of treatment. ESRD had 2 additional samples: immediately prior to and immediately after dialysis. Vz was measured in mL per kilogram body weight (mL/kg). PK parameter renal function group assignment criteria differed slightly from the criteria for safety and efficacy analyses (specifically for the SRI group). PK criteria: All participants with at least one pretreatment value = 90 mL/min were assigned to the NRF group. All those with at least one pretreatment value < 30 mL/min were assigned to the SRI group. All those with a screening diagnosis of ESRD, were assigned to the ESRD group.	Day 1 of Cycle 1 to 28 days post dose	No
Secondary	Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Who Died	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years	Yes
Secondary	Number of Participants With Persistent Elotuzumab Anti-drug Antibodies (ADA) and Number of Participants ADA Positive at Cycle 2 Pre-dose.	Serum samples were evaluated for the presence of ADAs using a validated bridging electrochemiluminescence (ECL) immunoassay. Samples in: Cycle 1, Day 1 0 h (pre-dose), Cycle 2, Day 1(Study Day 29), 0 h (pre-dose; 672 h post-dose), Cycle 3, Day 1, 0 h and in cylcle thereafter, at end of study/discontinuation, and at 30 and 60 day follow up visits post treatment. ADA Positive Participant: baseline negative with at least one ADA positive sample at any time after initiation of treatment or baseline positive with at least one ADA positive sample at any time after initiation of treatment with a titer 9-fold greater than the baseline; Persistent Positive: ADA positive at 2 or more sequential timepoints at least 12 weeks apart; Last Sample Positive: Not persistent positive and ADA Positive Sample in the last sampling timepoint; Other Positive: not persistent positive with ADA negative sample in the last sampling; ADA Negative: no ADA positive sample after the initiation of treatment.	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years	Yes
Secondary	Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years	Yes
Secondary	Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests	NCI CTCAE, version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years	Yes
Secondary	Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests	Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:	From first dose (Day 1) to last dose plus 60 days, up to Primary Endpoint (June 2014), approximately 2 years	Yes

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form