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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01985126
First received: July 22, 2013
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Daratumumab 16 mg/kg (Part 1)
Drug: Daratumumab 8 mg/kg (Part 1)
Drug: Methylprednisolone
Drug: Acetaminophen
Drug: Diphenhydramine
Drug: Daratumumab (Part 2)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Overall response rate following treatment with daratumumab [ Time Frame: Up to 6 months after the last participant is enrolled in the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT) [ Time Frame: Up to 30 days after the last dose of study medication ] [ Designated as safety issue: Yes ]
  • Duration of and time to response to daratumumab [ Time Frame: Up to 18 months after last participant receives first dose of study drug ] [ Designated as safety issue: No ]
  • Clinical benefit rate following treatment with daratumumab [ Time Frame: Up to 8 weeks after the last dose of daratumumab administered ] [ Designated as safety issue: No ]
  • Overall survival following treatment with daratumumab [ Time Frame: Up to 18 months after last participant receives first dose of study drug ] [ Designated as safety issue: No ]
  • Progression-free survival following treatment with daratumumab [ Time Frame: Up to 18 months after last participant receives first dose of study drug ] [ Designated as safety issue: No ]
  • Time to disease progression following treatment with daratumumab [ Time Frame: Up to 18 months after last participant receives first dose of study drug ] [ Designated as safety issue: No ]
  • Total systemic clearance of daratumumab [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Maximum observed concentration of daratumumab [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Minimum observed concentration of daratumumab [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Volume of distribution of daratumumab [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with generation of antibodies to daratumumab [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with soluble CD38 levels [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with complement inhibitory protein expression [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with antibody-dependent cell-mediated cytotoxicity expression [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]
  • Number of participants with complement-dependent cytotoxicity expression [ Time Frame: Up to post-treatment visit Week 8 ] [ Designated as safety issue: No ]

Enrollment: 125
Study Start Date: September 2013
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1
During Stage 1 of Part 1, participants will be randomized to receive daratumumab treatment regimens in Group A and Group B. If in Stage 1, 1 or both of the treatment groups is considered to be ineffective and/or not well tolerated, then that treatment group will be terminated. Participants in Group B will be given the option to cross over to Group A if the investigator deems it in the best interest of the participants.
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
Drug: Daratumumab 8 mg/kg (Part 1)
Daratumumab 8 mg/kg every 4 weeks (Q4W) continuously by intravenous infusion
Drug: 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
Drug: Acetaminophen
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
Drug: 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.
Experimental: Part 2
Based on the Part 1 response rate, Group A or B daratumumab treatment will be selected as the treatment regimen for participants enrolled in Part 2.
Drug: 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
Drug: Acetaminophen
650 to 1000 mg administered in prophylactic doses by mouth prior to study drug administration.
Drug: 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.
Drug: 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.

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 (18 months after last participant receives first dose of study drug), participants who are benefiting from treatment with daratumumab will have the option to continue treatment in Study 54767414MMY2002.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01985126

  Show 23 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01985126     History of Changes
Other Study ID Numbers: CR102651, 54767414MMY2002, 2013-000752-18
Study First Received: July 22, 2013
Last Updated: August 18, 2014
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Spanish Agency of Medicines

Keywords provided by Janssen Research & Development, LLC:
Multiple myeloma
Daratumumab
Proteasome inhibitor
Immunomodulatory drug
IMiD

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
Acetaminophen
Diphenhydramine
Methylprednisolone
Methylprednisolone Hemisuccinate
Promethazine
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Proteasome Inhibitors
Antibodies, Monoclonal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014