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

Janssen (J&J Innovative Medicine)

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma

Treatments

Drug: Daratumumab (Part 2)

Drug: Diphenhydramine

Drug: Daratumumab 8 mg/kg (Part 1)

Drug: Acetaminophen

Drug: Daratumumab 16 mg/kg (Part 1)

Drug: Methylprednisolone

Study type

Interventional

Funder types

Industry

Identifiers

NCT01985126

54767414MMY2002 (Other Identifier)

2013-000752-18 (EudraCT Number)

CR102651

Details and patient eligibility

About

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.

Full 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, participants who are benefiting from treatment with daratumumab will have the option to continue treatment.

Enrollment

124 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

124 participants in 2 patient groups

Part 1

Experimental group

Description:

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.

Treatment:

Drug: Diphenhydramine

Drug: Daratumumab 8 mg/kg (Part 1)

Drug: Methylprednisolone

Drug: Acetaminophen

Drug: Daratumumab 16 mg/kg (Part 1)

Part 2

Experimental group

Description:

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.

Treatment:

Drug: Diphenhydramine