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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 2

Conditions: Multiple Myeloma

Treatments: Drug: Part 2: Daratumumab; Other: Dexamethasone; Drug: Part 1: Daratumumab; Other: Methylprednisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00574288

CR101876

DARA-GEN501 (Other Identifier)

GEN501 (Other Identifier)

2007-003783-22 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

104 participants in 2 patient groups

Dose Escalation: Daratumumab

Experimental group

Treatment:

Other: Methylprednisolone

Drug: Part 1: Daratumumab

Dose Expansion: Daratumumab

Experimental group

Treatment:

Other: Dexamethasone

Other: Methylprednisolone

Drug: Part 2: Daratumumab