Clinical trial NCT01985126: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
Daratumumab
Proteasome inhibitor
Immunomodulatory drug
IMiD
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-11-15
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Overall Response
timeFrame: Up to 14.4 Months
Secondary outcomes:
measure: Duration of Response
timeFrame: Up to 14.4 Months
measure: Overall Survival
timeFrame: Approximately up to 3 years
measure: Percentage of Participants With Clinical Benefit
timeFrame: Up to 14.4 Months
measure: Time to Response
timeFrame: Up to 14.4 Months
measure: Progression Free Survival
timeFrame: Up to 14.4 Months
measure: Time to Disease Progression
timeFrame: Up to 14.4 Months
Other outcomes:
Locations:
city: Duarte
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Detroit
country: United States
state: Michigan
city: New Brunswick
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Halifax
country: Canada
state: Nova Scotia
city: Montreal
country: Canada
state: Quebec
city: Barcelona
country: Spain
city: Salamanca N/A
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Usmani SZ, Nahi H, Plesner T, Weiss BM, Bahlis NJ, Belch A, Voorhees PM, Laubach JP, van de Donk NWCJ, Ahmadi T, Uhlar CM, Wang J, Feng H, Qi M, Richardson PG, Lonial S. Daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma: final results from the phase 2 GEN501 and SIRIUS trials. Lancet Haematol. 2020 Jun;7(6):e447-e455. doi: 10.1016/S2352-3026(20)30081-8.
citation: Adams HC 3rd, Stevenaert F, Krejcik J, Van der Borght K, Smets T, Bald J, Abraham Y, Ceulemans H, Chiu C, Vanhoof G, Usmani SZ, Plesner T, Lonial S, Nijhof I, Lokhorst HM, Mutis T, van de Donk NWCJ, Sasser AK, Casneuf T. High-Parameter Mass Cytometry Evaluation of Relapsed/Refractory Multiple Myeloma Patients Treated with Daratumumab Demonstrates Immune Modulation as a Novel Mechanism of Action. Cytometry A. 2019 Mar;95(3):279-289. doi: 10.1002/cyto.a.23693. Epub 2018 Dec 11.
citation: Usmani SZ, Khan I, Chiu C, Foureau D, Druhan LJ, Rigby K, Casneuf T, Sasser AK. Deep sustained response to daratumumab monotherapy associated with T-cell expansion in triple refractory myeloma. Exp Hematol Oncol. 2018 Feb 7;7:3. doi: 10.1186/s40164-018-0096-7. eCollection 2018.
citation: Nijhof IS, Casneuf T, van Velzen J, van Kessel B, Axel AE, Syed K, Groen RW, van Duin M, Sonneveld P, Minnema MC, Zweegman S, Chiu C, Bloem AC, Mutis T, Lokhorst HM, Sasser AK, van de Donk NW. CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma. Blood. 2016 Aug 18;128(7):959-70. doi: 10.1182/blood-2016-03-703439. Epub 2016 Jun 15.
citation: Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, Belch A, Krishnan A, Vescio RA, Mateos MV, Mazumder A, Orlowski RZ, Sutherland HJ, Blade J, Scott EC, Oriol A, Berdeja J, Gharibo M, Stevens DA, LeBlanc R, Sebag M, Callander N, Jakubowiak A, White D, de la Rubia J, Richardson PG, Lisby S, Feng H, Uhlar CM, Khan I, Ahmadi T, Voorhees PM. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016 Apr 9;387(10027):1551-1560. doi: 10.1016/S0140-6736(15)01120-4. Epub 2016 Jan 7.