An Efficacy and Safety Study of Daratumumab in Patients With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor [PI] and Immunomodulatory Drug [IMiD]) or Are Double Refractory to a PI and an IMiD

Multiple Myeloma Clinical Trial

Official title:

An Open-label, Multicenter, Phase 2 Trial Investigating the Efficacy and Safety of Daratumumab in Subjects With Multiple Myeloma Who Have Received at Least 3 Prior Lines of Therapy (Including a Proteasome Inhibitor and IMiD) or Are Double Refractory to a Proteasome Inhibitor and an IMiD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01985126
• Other study ID #: CR102651
• Secondary ID: 54767414MMY20022
• Status: Completed
• Phase: Phase 2
• Start date: September 27, 2013
• Est. completion date: May 30, 2017

Study information

• Verified date: June 2018
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of 2 daratumumab treatment regimens in participants with multiple myeloma who have received at least 3 prior lines of therapy (including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or are double refractory to a PI and an IMiD.

Description:

This is an open-label (identity of assigned study drug will be known) study of daratumumab for the treatment of participants with multiple myeloma who have received at least 3 prior lines of therapy including a PI and an IMiD or whose disease is double refractory to both a PI and an IMiD. Up to approximately 150 participants are to be enrolled. The study includes screening, treatment, and follow-up phases. Participants will receive daratumumab by intravenous infusion (28-day cycles) until disease progression, unacceptable toxicity, or other protocol-defined reasons. For all study drug administrations, participants will receive pre- and post-infusion medications for the prevention of infusion related reactions. Follow-up will continue until death, loss to follow up, consent withdrawal for study participation, or study end, whichever occurs first. The study will consist of 2 sequential parts (Part 1 and Part 2). The purpose of Part 1 is to select a dose and schedule for Part 2 of the study. Assessment of tumor response and disease progression will be conducted according to IMWG response criteria. Serial pharmacokinetic blood samples and a pharmacogenomic blood sample will be collected. Safety will be monitored throughout the study. At the end of the study, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: May 30, 2017
• Est. primary completion date: January 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented multiple myeloma according to protocol-defined criteria

• Evidence of disease progression on the most recent prior treatment regimen based on International Myeloma Working Group criteria

• Eastern Cooperative Oncology Group performance status score of 0, 1, or 2

• Laboratory values and electrocardiogram within protocol-defined parameters at screening

Exclusion Criteria:

• Received daratumumab or other anti-CD38 therapies previously

• Nonsecretory multiple myeloma

• Previously received an allogenic stem cell transplant or has received an autologous stem cell transplantation within 12 weeks

• Exhibiting clinical signs of meningeal involvement of multiple myeloma

• Known chronic obstructive pulmonary disease, persistent asthma, or a history of asthma within 5 years

• Seropositive for human immunodeficiency virus, hepatitis B or antibodies to hepatitis B surface and core antigens, or hepatitis C

• Has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab 16 mg/kg (Part 1)
Daratumumab 16 mg/kg administered at weekly intervals (QW) for 8 weeks, then every 2 weeks (Q2W) for an additional 16 weeks, then every 4 weeks (Q4W) thereafter by intravenous infusion
• Daratumumab 8 mg/kg (Part 1)
Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion
• Methylprednisolone
Administered in prophylactic doses intravenously (or equivalent in accordance with local standards) prior to and after study drug administration. Intravenous administration is preferred, but oral steroids may be substituted
• Acetaminophen
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
• Diphenhydramine
25 to 50 mg administered in prophylactic doses by mouth (or equivalent in accordance with local standards) prior to and after study drug administration.
• Daratumumab (Part 2)
Based on the Part 1 response rate, Group A or B treatment will be selected as the treatment regimen for participants enrolled in Part 2.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Canada,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Overall Response	Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.	Up to 14.4 Months
Secondary	Duration of Response	Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in IMWG criteria. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component (the absolute increase must be >=0.5 g/dL) and/or; urine M-component (the absolute increase must be >=200 mg/24 hours) and/or; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 milligram per deciliter (mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 millimole per liter [mmol/L]) that can be attributed solely to the plasma cell proliferative disorder.	Up to 14.4 Months
Secondary	Overall Survival	Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.	Approximately up to 3 years
Secondary	Percentage of Participants With Clinical Benefit	Clinical benefit rate defined as percentage of participants who achieved minimal response (MR) or better. MR: >=25% but <= 49% reduction of serum M-protein and reduction in urine M-protein by 50%-89%. If present at baseline 25% to 49% reduction in size of soft tissue plasmacytomas.	Up to 14.4 Months
Secondary	Time to Response	Time to response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better).	Up to 14.4 Months
Secondary	Progression Free Survival	Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.	Up to 14.4 Months
Secondary	Time to Disease Progression	Time to progression was defined as the number of days from the date of first dose of daratumumab to the date of first record of disease progression.	Up to 14.4 Months