Daratumumab in Combination With Lenalidomide and Dexamethasone in Relapsed and Relapsed-refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01615029
First received: June 6, 2012
Last updated: February 9, 2015
Last verified: February 2015
  Purpose

The purpose of this study is to establish the safety profile of daratumumab when given in combination with Lenalidomide and dexamethasone in participants with relapsed or relapsed and refractory Multiple Myeloma (MM).


Condition Intervention Phase
Multiple Myeloma
Drug: Part 1 (Dose Escalation): Daratumumab
Drug: Part 2 (Dose Expansion): Daratumumab
Drug: Lenalidomide
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, International, Multicenter, Dose Escalating Phase I/II Trial Investigating the Safety of Daratumumab in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Relapsed and Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Part 1 and 2: Number of participants with adverse events [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Part 1 and 2: Number of participants with objective response [ Time Frame: Up to cycle 24 (approximately 24 months) ] [ Designated as safety issue: No ]
    Objective response rate (ORR) will be measured using the international uniform response criteria for multiple myeloma. ORR is defined as the number of participants with tumor size reduction of a predefined amount and for a minimum time period. The subcategories of ORR are complete response, stringent complete response, very good partial response, partial response, minimal response, and stable disease. ORR is sum of complete and partial responses.

  • Part 1 and 2: Area under the concentration-time curve of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Maximum observed concentration of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Minimum observed concentration of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Time to reach the maximum plasma concentration of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Apparent clearance of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Volume of distribution of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Half-life of daratumumab [ Time Frame: Predose, and up to 12 hours for Cycle 1; predose and up to 2 hrs for Cycle 2; predose and end of daratumumab infusion for Cycles 3 to 24; monthly for follow-up visits (up to 6 months); and at end of treatment visit (approximately month 30) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Time taken for progression of disease [ Time Frame: Up to cycle 24 (approximately 24 months) ] [ Designated as safety issue: No ]
  • Part 1 and 2: Duration of response [ Time Frame: Up to cycle 24 (approximately 24 months) ] [ Designated as safety issue: No ]
    Response duration is defined as the number of days from the first observation where the participant meets the criteria for response to the time where the participant's disease progresses.

  • Part 1 and 2: Participants with progression free survival [ Time Frame: Up to cycle 24 (approximately 24 months) ] [ Designated as safety issue: No ]
    Progression free survival is the time period from start of study medication till the disease progression or death, whichever occurs first.


Enrollment: 45
Study Start Date: January 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daratumumab
Participants will receive daratumumab along with Lenalidomide and dexamethasone.
Drug: Part 1 (Dose Escalation): Daratumumab
Participants will receive intravenous (injection of a substance into a vein) infusion of daratumumab in an increased fashion from 2 milligram per kilogram (mg/kg) up to maximum dose of 16 mg/kg. Considering the safety and efficacy of dose in Part 1, recommended phase 2 dose (RP2D) for Part 2 of the study will be decided. A predose infusion of 10 percent (%) of the full dose of daratumumab will be administered a day before the first full infusion of the first cycle. Participants will receive 4 weekly infusions in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and from cycles 7 to 24 monthly infusions will be administered.
Drug: Part 2 (Dose Expansion): Daratumumab
Participants will receive RP2D as determined in Part 1 of the study. Participants will receive 4 weekly infusions of RP2D in the first 2 treatment cycles. From cycles 3 to 6 infusions will be administered every alternate week and from cycles 7 to 24 monthly infusions will be administered.
Drug: Lenalidomide
All participants (Part 1 and Part 2) will receive 25 mg lenalidomide orally (by mouth) from days 1 to 21 of each 28-day cycle until disease progression.
Drug: Dexamethasone
All participants (Part 1 and Part 2) will receive 40 mg (20 mg intravenously [injection of a substance into a vein] before the daratumumab infusion and 20 mg orally after daratumumab infusion) dexamethasone once weekly. Participants older than 75 years or underweight (body mass index [BMI] less than [<] 18.5), the dexamethasone dose will be administered at a dose of 20 mg once weekly until disease progression.

Detailed Description:

The study is conducted in two parts. The dose escalation portion of the trial (Part 1) participants are enrolled into cohorts at increasing dose levels of daratumumab in combination with Len/Dex in 28 day treatment cycles. Part 2, the cohort expansion part of the trial, will further explore the maximum tolerated dose (MTD) (or the maximum tested dose) of daratumumab as determined in Part 1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • (Part 1) Have relapsed multiple myeloma after receiving a minimum of 2 and a maximum of 4 prior lines of therapy and be eligible for treatment with lenalidomide and dexamethasone (Len/Dex)
  • (Part 2) Have received at least 1 prior line of therapy for multiple myeloma
  • Be older than or be 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status (0-2)
  • Provide signed informed consent after receipt of oral and written information about the study and before any study-related activity is performed

Exclusion Criteria:

  • Have previously received an allogenic stem cell transplant
  • Have received autologous stem cell transplant within 12 weeks before the first infusion
  • Have received antimyeloma treatment, radiotherapy, or any experimental drug or therapy within 2 weeks before the first infusion
  • Have received a cumulative dose of corticosteroid greater than or equal to (>=) 200 milligram (mg) (dexamethasone, or equivalent doses of prednisone) within 2 weeks before the first infusion
  • Have discontinued lenalidomide due to any treatment-related adverse event or be refractory to any dose of lenalidomide. Refractory to lenalidomide is defined as either, participants whose disease progresses within 60 days of lenalidomide, or participants whose disease is nonresponsive while on any dose of lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an minimal response (MR) or development of progressive disease (PD) while on lenalidomide
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01615029

Locations
United States, Massachusetts
Boston, Massachusetts, United States
Denmark
Copenhagen Ø, Denmark
Vejle, Denmark
France
Lille Cedex, France
Nantes N/A, France
Vandoeuvre Les Nancy, France
Netherlands
Utrecht, Netherlands
United Kingdom
London, United Kingdom
Manchester, United Kingdom
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Principal Investigator: Torben Plesner, MD Vejle Hospital
Principal Investigator: Paul Richardson, MD Dana Farber
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01615029     History of Changes
Other Study ID Numbers: CR101391, GEN503, DARA-GEN503, 2011-005709-62
Study First Received: June 6, 2012
Last Updated: February 9, 2015
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Daratumumab
Lenalidomide
Dexamethasone
Dose-escalation
Relapsed multiple myeloma
Relapsed and refractory multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Antibodies, Monoclonal
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on March 26, 2015