ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02076009
Recruitment Status : Active, not recruiting
First Posted : March 3, 2014
Results First Posted : February 10, 2017
Last Update Posted : April 2, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to compare the effectiveness of daratumumab when combined with lenalidomide and dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free survival in participants with relapsed or refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: Lenalidomide Drug: Dexamethasone Phase 3

Detailed Description:
This is a randomized (participants will be assigned by chance to study treatments), open-label (all participants and study personnel will know the identity of the study treatments), active-controlled (none of the study treatments are placebo), parallel-group (both treatment arms will run at the same time), multicenter study. In this study, daratumumab, lenalidomide, and low-dose dexamethasone (DRd) will be compared with lenalidomide and low dose dexamethasone (Rd) in participants with relapsed or refractory multiple myeloma. Participants will be randomized in a 1:1 ratio to receive either DRd or Rd. The study will include a Screening Phase, a Treatment Phase (involving treatment cycles of approximately 28 days in length), and a Follow-up Phase. The Treatment Phase will extend from the administration of the first dose of study medication until disease progression or unacceptable toxicity. Participants will also discontinue study treatment if: they become pregnant; have their dose held for more than 28 days (or if 3 consecutive planned doses of daratumumab are missed for reasons other than toxicity); or for safety reasons (for example, adverse event). The Follow-up Phase will begin at the end of treatment and will continue until death, loss to follow-up, consent withdrawal for study participation, or study end, whichever occurs first. Eligible participants from Rd group who have had sponsor-confirmed disease progression will be offered the option for treatment with daratumumab monotherapy (of 28 days cycle). The primary endpoint will be progression-free survival (PFS). Analysis of the primary endpoint is anticipated to be performed at approximately 18 months after participant's first dose. Study end is anticipated at approximately 6 years after the last participant is randomized. Blood and urine samples will be obtained at time points during the study, together with bone marrow aspirates/biopsies and skeletal surveys. Participant safety will be assessed throughout the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 569 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : May 23, 2014
Actual Primary Completion Date : March 7, 2016
Estimated Study Completion Date : September 29, 2020


Arm Intervention/treatment
Experimental: Daratumumab + lenalidomide + dexamethasone
During each 28-day treatment cycle, participants will receive daratumumab, lenalidomide, and dexamethasone.
Drug: Daratumumab
Daratumumab 16mg/kg will be administered as an intravenous (IV) infusion (into the vein) as per the following schedule: once a week during treatment cycles 1 and 2; every 2 weeks during treatment cycles 3 to 6; and every 4 weeks for cycles 7 and onwards.

Drug: Lenalidomide
Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.

Drug: Dexamethasone
Dexamethasone (or equivalent in accordance with local standards) will be administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 18.5).

Active Comparator: Lenalidomide + dexamethasone
During each 28-day treatment cycle, participants will receive lenalidomide and dexamethasone.
Drug: Lenalidomide
Lenalidomide will be administered at a dose of 25 mg orally (by mouth) on Days 1 through 21 of each treatment cycle.

Drug: Dexamethasone
Dexamethasone (or equivalent in accordance with local standards) will be administered as a total dose of 40 mg weekly (or 20 mg weekly for participants > 75 years old or with a body mass index < 18.5).

Active Comparator: Daratumumab monotherapy
During each 28-day treatment cycle, participants will receive daratumumab alone in daratumumab monotherapy group.
Drug: Daratumumab
Daratumumab 16mg/kg will be administered as an intravenous (IV) infusion (into the vein) as per the following schedule: once a week during treatment cycles 1 and 2; every 2 weeks during treatment cycles 3 to 6; and every 4 weeks for cycles 7 and onwards.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: From randomization to either disease progression or death whichever occurs first until 3 years ]
    PFS was defined as duration from date of randomization to either progressive disease (PD)/death, whichever occurred first. PD was defined as meeting any one of following criteria: Increase of greater than equal to (>=)25 percent (%) 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-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; 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 >10 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.


Secondary Outcome Measures :
  1. Time to Disease Progression (TTP) [ Time Frame: From randomization to disease progression until 3 years ]
    TTP was defined as time from date of randomization to date of first documented evidence of progressive disease (PD). PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5 g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200 mg/24hours; Only in participants without measurable serum and urine M-protein levels: increase of >=25% in difference between involved and uninvolved free light chain (FLC) levels from lowest response value and absolute increase must be >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 Plasma Cell (PC) proliferative disorder.

  2. Percentage of Participants Who Achieved Very Good Partial Response (VGPR) or Better [ Time Frame: From randomization to disease progression (approximately up to 3 years) ]
    VGPR or better is defined as the percentage of participants who achieved VGPR, complete response (CR) and stringent complete response (sCR) according to the International Myeloma Working Group criteria (IMWG). IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or >=90% reduction in serum M-protein plus urine M-protein <100 mg/24 hours, if the serum and urine M-protein are not measurable, a decrease of >90% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required; CR: Negative immunofixation on the serum and urine, disappearance of any 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.

  3. Percentage of Participants With Negative Minimal Residual Disease (MRD) [ Time Frame: From randomization to the date of first documented evidence of PD until 3 years ]
    Minimal residual disease was assessed for all participants who achieved a complete response (CR) or stringent complete response (sCR). The MRD negativity rate was defined as the percentage of participants who had negative MRD assessment at any time point after the first dose of study drugs by evaluation of bone marrow aspirates or whole blood at 10^- 4 threshold.

  4. Overall Response Rate [ Time Frame: From randomization to disease progression (approximately up to 3 years) ]
    Overall response rate was defined as the percentage of participants who achieved a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria, during or after study treatment. IMWG criteria for 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, in addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

  5. Overall Survival (OS) [ Time Frame: Up to approximately 5 years (anticipated) after the last participant is randomized ]
    Overall survival was measured from the date of randomization to the date of the participant's death.

  6. Time to Response [ Time Frame: From randomization up to first documented CR or PR until 3 years ]
    Time to response was defined as the time between the date of randomization and the first efficacy evaluation that the participant met all criteria for partial response (PR) or better.

  7. Duration of Response (DOR) [ Time Frame: From randomization to the date of first documented evidence of PD until 3 years ]
    DOR was defined for participants with confirmed response (PR or better) as time between first documentation of response and disease progression/death due to PD, whichever occurs first. PD was defined as meeting any one of following criteria: Increase of >=25% in level of serum M-protein from lowest response value and absolute increase must be >=0.5g/dL; Increase of >=25% in 24-hour urinary light chain excretion (urine M-protein) from lowest response value and absolute increase must be >=200mg/24hours; 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 >10mg/dL; Definite increase in size of existing bone lesions/soft tissue plasmacytomas; Definite development of new bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium >11.5mg/dL) that can be attributed solely to PC proliferative disorder.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Must have documented multiple myeloma and measurable disease
  • Must have received at least 1 prior line of therapy for multiple myeloma and achieved a response (partial response or better) to at least one prior regimen
  • Must have documented evidence of progressive disease as defined by the International Myeloma Working Group criteria on or after their last regimen
  • Must have an Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2
  • If a participant has received subsequent anticancer therapy (salvage therapy), the participant must have a "wash-out period" defined as 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the planned start date of daratumumab monotherapy. The only exception is the emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 milligram per day for a maximum of 4 days) before Daratumumab monotherapy

Exclusion Criteria:

  • Has received any of the following therapies: daratumumab or other anti-CD38 therapies
  • Has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment
  • Disease shows evidence of refractoriness or intolerance to lenalidomide or if previously treated with a lenalidomide-containing regimen the participant is excluded if he or she discontinued due to any adverse event related to prior lenalidomide treatment
  • Has received autologous stem cell transplantation within 12 weeks before the date of randomization, or previously received an allogenic stem cell transplant (regardless of timing), or planning to undergo a stem cell transplant prior to progression of disease
  • History of malignancy (other than multiple myeloma) within 5 years before the first dose of daratumumab monotherapy (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02076009


  Hide Study Locations
Locations
United States, Arkansas
Little Rock, Arkansas, United States
United States, Florida
Gainesville, Florida, United States
West Palm Beach, Florida, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Iowa
Iowa City, Iowa, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Louisiana
Baton Rouge, Louisiana, United States
New Orleans, Louisiana, United States
United States, Maryland
Bethesda, Maryland, United States
Columbia, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New Jersey
New Brunswick, New Jersey, United States
United States, New York
New York, New York, United States
United States, North Carolina
Charlotte, North Carolina, United States
United States, Oregon
Eugene, Oregon, United States
United States, South Carolina
Spartanburg, South Carolina, United States
United States, Texas
Austin, Texas, United States
Dallas, Texas, United States
Houston, Texas, United States
United States, Virginia
Fairfax, Virginia, United States
Australia
Camperdown, Australia
Geelong, Australia
Heidelberg, Australia
Malvern, Australia
South Brisbane, Australia
Southport, Australia
Belgium
Antwerpen, Belgium
Brussel, Belgium
Edegem, Belgium
Gent, Belgium
Kortrijk, Belgium
Leuven, Belgium
Liege, Belgium
Canada, Alberta
Calgary, Alberta, Canada
Edmonton, Alberta, Canada
Canada, British Columbia
Vancouver, British Columbia, Canada
Canada, Nova Scotia
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton, Ontario, Canada
London, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
Quebec City, Quebec, Canada
Canada
Surrey N/A, Canada
Toronto N/A, Canada
Denmark
Copenhagen, Denmark
Odense, Denmark
Vejle, Denmark
France
Argenteuil, France
Caen, France
Lille, France
Limoges, France
Nantes Cedex 1, France
Paris, France
Pessac, France
Pierre Benite, France
Rennes, France
Toulouse Cedex 9, France
Tours Cedex 9, France
Vandoeuvre Les Nancy, France
Germany
Berlin, Germany
Bonn, Germany
Hamburg, Germany
Hamm, Germany
Heidelberg, Germany
Jena, Germany
Karlsruhe, Germany
Koblenz, Germany
Köln, Germany
Saarbrücken, Germany
Villingen-Schwenningen, Germany
Greece
Athens Attica, Greece
Israel
Haifa, Israel
Jerusalem, Israel
Nahariya, Israel
Netanya, Israel
Petah Tikva, Israel
Ramat Gan, Israel
Tel Aviv, Israel
Japan
Hitachi, Japan
Kanazawa, Japan
Kobe, Japan
Kurume, Japan
Matsuyama, Japan
Nagoya, Japan
Narita, Japan
Ohgaki, Japan
Okayama, Japan
Osaka, Japan
Sendai, Japan
Shibukawa, Japan
Tachikawa, Japan
Tokyo, Japan
Korea, Republic of
Gyeonggi-Do, Korea, Republic of
Incheon, Korea, Republic of
Seoul, Korea, Republic of
Netherlands
Amsterdam, Netherlands
Rotterdam, Netherlands
Utrecht, Netherlands
Zwolle, Netherlands
Poland
Brzozow, Poland
Chorzów, Poland
Gdansk, Poland
Legnica, Poland
Lublin, Poland
Poznan, Poland
Slupsk, Poland
Wroclawa, Poland
Russian Federation
Dzerzhinsk, Russian Federation
Ekaterinburg, Russian Federation
Moscow, Russian Federation
Nizhny Novgorod, Russian Federation
Petrozavodsk, Russian Federation
Ryazan, Russian Federation
Samara, Russian Federation
St-Petersburg, Russian Federation
St. Petersburg, Russian Federation
Syktyvkar, Russian Federation
Spain
Badalona, Spain
Barcelona, Spain
La Laguna (Santa Cruz De Tenerife), Spain
Madrid, Spain
Pamplona, Spain
Salamanca N/A, Spain
Sevilla, Spain
Sweden
Falun, Sweden
Göteborg, Sweden
Helsingborg, Sweden
Huddinge, Sweden
Lund, Sweden
Stockholm, Sweden
Uppsala, Sweden
Taiwan
Changhua, Taiwan
Taichung City, Taiwan
Tainan, Taiwan
Taipei, Taiwan
Taoyuan, Taiwan
United Kingdom
Birmingham, United Kingdom
Leeds, United Kingdom
London, United Kingdom
Oxford, United Kingdom
Southampton, United Kingdom
Surrey, United Kingdom
Wolverhampton, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02076009     History of Changes
Other Study ID Numbers: CR103663
54767414MMY3003 ( Other Identifier: Janssen Research & Development, LLC )
2013-005525-23 ( EudraCT Number )
First Posted: March 3, 2014    Key Record Dates
Results First Posted: February 10, 2017
Last Update Posted: April 2, 2018
Last Verified: March 2018

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Daratumumab
Lenalidomide
Dexamethasone

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
Dexamethasone acetate
Dexamethasone
Lenalidomide
Daratumumab
Thalidomide
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists