A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent

Multiple Myeloma Clinical Trial

Official title:

A Prospective, Single-Arm, Multicenter, Pragmatic Phase-IV Trial Investigating Safety and Effectiveness of DARZALEX (Daratumumab) In Indian Subjects With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03768960
• Other study ID #: CR108556
• Secondary ID: 54767414MMY4008
• Status: Completed
• Phase: Phase 4
• Start date: June 10, 2019
• Est. completion date: July 16, 2022

Study information

• Verified date: August 2022
• Source: Johnson & Johnson Private Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate the safety profile of daratumumab in routine clinical practice when given as monotherapy in Indian participants with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: July 16, 2022
• Est. primary completion date: July 16, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with relapsed and refractory multiple myeloma (as per International Myeloma Working Group [IMWG] definitions) whose prior therapy included a proteasome inhibitor and an immunomodulatory agent, being newly initiated on DARZALEX (daratumumab) monotherapy based on independent clinical judgment of treating physicians as per locally approved prescribing information

• Each participant (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Participants must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the informed consent form (ICF)

Exclusion Criteria:

• Participants who are not eligible to receive DARZALEX as per the locally approved prescribing information

• Participant participating or planning to participate in any interventional drug trial during the course of this study

• Known seropositive for human immunodeficiency virus (HIV)

• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection (that is, participants who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. exception: Participants with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR

• Known seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab
Participants will receive 16 mg/kg of daratumumab as IV infusion QW in Cycles 1 and 2 (Days 1, 8, 15 and 22) and Q2W in Cycle 3 to 6 (Days 1 and 15).

Locations

Country	Name	City	State
India	Avron Hospitals Pvt. Ltd	Ahmedabad
India	M S Ramaiah Medical College and Hospital	Bengaluru
India	Sparsh Hospitals & Critical Care (Pvt) Ltd	Bhubaneshwar
India	Apollo Hospitals	Bhubaneswar
India	Post Graduate Institute of Medical Education & Research (PGIMER)	Chandigarh
India	Apollo Hospitals	Hyderabad
India	Basavatarakam Indo-American Hospital	Hyderabad
India	Cytecare Hospitals Pvt. Ltd	Karnataka
India	Tata Medical Center	Kolkata
India	Shatabdi Super Speciality Hospital	Mumbai Naka
India	Kingsway Hospital	Nagpur
India	Apex Wellness Hospital	Nashik
India	All India Institute of Medical Sciences	New Delhi
India	Jawaharlal Institute of Postgraduate Medical Education and Research	Pondicherry
India	Deenanath Mangeshkar Hospital and Research Centre	Pune
India	Noble Hospital Pvt Ltd	Pune

Sponsors (1)

Lead Sponsor	Collaborator
Johnson & Johnson Private Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment Emergent Adverse Events (TEAE)	An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug.	Approximately up to 29 weeks
Secondary	Overall Response Rate (ORR)	ORR- % of participants who achieve partial response (PR) or better per IMWG criteria during study treatment. PR: >=50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to<200mg/24hour; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chain (FLC) level; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC% >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas; VGPR: serum and urine M-component detectable by immunofixation or >=90% reduction in serum M-protein and urine M-protein <100mg/24hour; Complete response(CR):negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% PCs in bone marrow; sCR: CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.	Approximately up to 24 weeks
Secondary	Percentage of Participants with Very Good Partial Response (VGPR) or better	VGPR or better is defined as percentage (%) of participants with a response of very good partial response (VGPR) or better according to the International Myeloma Working Group (IMWG) criteria, during the study treatment. IMWG criteria for VGPR: serum and urine M-component detectable by immunofixation or greater than or equal to (>=)90% reduction in serum M-protein and urine M-protein less than (<)100 milligram(mg)/24hour; CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow; Stringent CR (sCR): CR and normal FLC ratio, absence of clonal PCs by immunohistochemistry, immunofluorescence or 2 to 4 color flow cytometry.	Approximately up to 24 weeks
Secondary	Percentage of Participants with Progression Free Survival (PFS)	PFS is defined as % of participants with PFS from date of randomization to either PD, according to the IMWG criteria or death, whichever occurs first. PD: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 gram per deciliter (g/dL); Increase of >=25% in 24 hours urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24 hour; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved FLC levels from lowest response value and absolute increase must be greater than (>)10 milligram per deciliter (mg/dL); Definite increase in size of existing bone lesions or soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.	Approximately up to 24 weeks
Secondary	Time to Response	Time to Response: time between the date of randomization and the first effectiveness evaluation that the participant has met all criteria for CR or PR. CR: negative immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% PCs in bone marrow; PR: greater than or equal to (>=) 50% reduction of serum M-protein, >=90% reduction in 24 hour urinary M-protein or to less than (<) 200 mg/24 hours; if serum and urine M-protein are not measurable, >=50% decrease in difference between involved and uninvolved free light chains (FLC) levels; if serum and urine M-protein and serum free light assay is not measurable, >=50% reduction in bone marrow plasma cell (PC), with baseline bone marrow PC percentage >=30%; if present at baseline, >=50% reduction in size of soft tissue plasmacytomas.	Approximately up to 24 weeks
Secondary	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score	The EORTC QLQ-C30 is a 30-item questionnaire containing both single and multi-item measures. These include five functional scales (Physical, Role, Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and Nausea/Vomiting), a Global Health Status/ Quality-of-Life (QoL) scale, and six single items (Constipation, Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The scores ranges from 0-100, a high score for functional scales and for Global Health Status/QoL represent better functioning ability or Health-Related Quality-of-Life (HRQoL), whereas a high score for symptom scales and single items represents significant symptomatology.	Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)
Secondary	Change from Baseline in EuroQol-5 Dimensions (EQ-5D-5L) Score	EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems and extreme problems) that reflect increasing levels of difficulty. The responses to the 5 dimensions are used to compute a single utility score ranging from zero (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual.	Baseline, Day 1 (Cycle 1 to 5); Days 1 and 28 (Cycle 6) (each cycle of 28 days)