Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00574288
First received: December 14, 2007
Last updated: July 15, 2015
Last verified: July 2015
  Purpose

Establishment of safety profile of HuMax-CD38 when given as monotherapy in participants with multiple myeloma relapsed from or refractory to at least 2 different cytoreductive therapies and without further established treatment options.


Condition Intervention Phase
Multiple Myeloma
Drug: Part 1: Daratumumab
Drug: Part 2: Daratumumab
Other: Methylprednisolone
Other: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma - Open Label, Dose-escalation Followed by Open Label, Single-arm Study

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Part 1 and 2: Adverse Events [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 27 (for Part 2) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.


Secondary Outcome Measures:
  • Part 1 and 2: Pharmacokinetic Parameters Based on Serum/Plasma Concentrations of Daratumumab [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 99 (for Part 2) ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters include maximum observed concentration (Cmax), time to reach the maximum plasma concentration (tmax) and Area under the concentration-time curve (AUC) of daratumumab.

  • Part 1 and 2: Objective Response [ Time Frame: Up to Week 28 (for Part 1) and Week 27 (for Part 2) ] [ 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: Relative Reduction in M-protein [ Time Frame: Up to Week 28 (for Part 1) and Week 27 (for Part 2) ] [ Designated as safety issue: No ]
    Relative reduction in M-protein will be assessed by measuring levels of M-protein.

  • Part 1 and 2: Time to Progression [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 99 (for Part 2) ] [ Designated as safety issue: No ]
    Time to progression is defined as the number of days from date of first full dose (Visit 2 in Part 1, or Visit 1 or 2 depending on the cohort in Part 2) to first disease progression.

  • Part 1 and 2: Duration of Response [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 99 (for Part 2) ] [ 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: Progression Free Survival [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 99 (for Part 2) ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the number of days from Day 0 to first disease progression or death.

  • Part 1 and 2: Overall Survival [ Time Frame: Up to Week 28 (for Part 1) and Up to Week 99 (for Part 2) ] [ Designated as safety issue: No ]
    Overall survival is defined as the number of days from Day 0 to death.

  • Adverse events. Relative reduction in M-component. Time to progression. Duration of response. Progression Free Survival. Overall Survival. [ Time Frame: Up to End of the Treatment (1 to 6 Weeks After the Last Infusion of Study Drug) ] [ Designated as safety issue: Yes ]
    An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.


Enrollment: 104
Study Start Date: March 2008
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation: Daratumumab Drug: Part 1: Daratumumab
First participant will receive intravenous (injection of a substance into a vein) 0.005 milligram per kilogram (mg/kg) (planned dose) infusion of daratumumab and other participants will receive different doses. The participants will receive 7 full infusions of daratumumab and 2 predose infusions every 2 weeks. The dose of daratumumab will be escalated sequentially and considering the safety and efficacy of dose in Part 1, dose for Part 2 of the study will be decided. A predose infusion of 10% of the full dose of daratumumab will be administered a day before the first 2 full infusions.
Other Name: HuMax-CD38
Other: Methylprednisolone

Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.

Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.

Experimental: Dose Expansion: Daratumumab Drug: Part 2: Daratumumab
In Part 2, the participants will receive dose of daratumumab as determined in part 1 (16 mg/kg) of the study. Participants will receive 8 full infusions at weekly intervals followed by biweekly (every 2 weeks) infusions for 16 additional weeks and monthly infusions until disease progression or unmanageable toxicity, whichever comes first. Predose was dropped at some point in Part 2. A predose infusion of 10 mg daratumumab will be administered on the day before the first full infusion in select cohorts.
Other Name: HuMax-CD38
Other: Methylprednisolone

Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.

Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.

Other: Dexamethasone
Participants (Part 2) will receive 20 mg dexamethasone intravenous (IV) injection pre-dose, on the first and second days after every full-dose infusions.

Detailed Description:

This study is conducted in two parts. In part I, participants are enrolled into cohorts at increasing dose levels. Participant safety and efficacy during part I will determine the doses used for Part II. In part II participants will be enrolled into one of two sequential treatment arms using two of the doses defined in part 1 of the study. Part II was 5 cohorts, 3 with 8 milligram per kilogram (mg/kg) and 2 with 16 mg/kg. Part I and all but the last cohort in Part II were dosed with Phase 1/ 2 drug product. The last cohort in Part II was dosed with Phase 3 drug product. Both Part I and Part II are open-label/unmasked.

  Eligibility

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

Inclusion criteria

  • Diagnosis of multiple myeloma (MM) requiring systemic therapy
  • Age greater than or equal to (>=) 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Life expectancy greater than (>) 3 months
  • Relapsed from or refractory to two or more different prior therapies
  • Signed Informed consent

Exclusion criteria

  • Plasma cell leukemia defined as a plasma cell count > 2000/millimeter^3 (mm^3)
  • Known amyloidosis
  • Participants who previously have received an allogeneic stem cell transplant
  • Sensory or motor neuropathy of >= grade 3
  • Past or current malignancy
  • Chronic or ongoing active infectious disease
  • Clinically significant cardiac disease
  • Significant concurrent, uncontrolled medical condition including, but not limited to, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
  • A baseline QT interval as corrected by Fridericia's formula > 470 millisecond (msec) for female participants or > 450 msec for male participants or a complete left bundle branch block (defined as a QRS interval >= 120 msec in left bundle branch block form)
  • Hypokalemia
  • Clinical signs of meningeal involvement of MM
  • Known severe chronic obstructive pulmonary disease or asthma defined as forced expiratory volume in 1 second (FEV1) less than (<) 60 percentage (%) of expected
  • History of significant cerebrovascular disease
  • Known Human Immunodeficiency Virus seropositivity
  • Positive serology for hepatitis B
  • Screening laboratory values
  • Concomitant corticosteroid
  • Other chemotherapy that is or may be active against myeloma within 3 weeks prior to Visit 2 (Part 1) or the first dose of daratumumab (Part 2). However, corticosteroid for myeloma (less than a 4-day course) could be administered within 1 week before Visit 2 (Part 1) or the first dose of daratumumab (Part 2)
  • Known hypersensitivity to components of the investigational product or severe allergic or anaphylactic reactions to humanized products
  • Participants who have received treatment with any nonmarket drug substance within 4 weeks before the first dose of daratumumab
  • Current participation in any other interventional clinical trial
  • Participants known or suspected of not being able to comply with a trial protocol (example, due to alcoholism, drug dependency, or psychological disorder)
  • Breastfeeding women or women with a positive pregnancy test at Screening
  • Women of childbearing potential not willing to use adequate contraception, defined as hormonal birth control or intrauterine device, during the trial and for 1 year after the last dose of daratumumab. For participants in the United States, the use of a double-barrier method is also considered adequate
  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: NCT00574288

Locations
United States, Massachusetts
Boston, Massachusetts, United States
Denmark
Copenhagen Ø, Denmark
Vejle, Denmark
Netherlands
Amsterdam, Netherlands
Utrecht, Netherlands
Sweden
Huddinge, Sweden
Lund, Sweden
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: NCT00574288     History of Changes
Other Study ID Numbers: CR101876, GEN501, DARA-GEN501
Study First Received: December 14, 2007
Last Updated: July 15, 2015
Health Authority: United States: Food and Drug Administration
Denmark: Danish Medicines Agency
Sweden: Medical Products Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Daratumumab
Safety
HuMax-CD38
Dose-escalation

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
Dexamethasone
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 01, 2015