Clinical trial NCT03242889: A Study of Subcutaneous Delivery of JNJ-54767414 (Daratumumab) in Japanese Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 1 Study of Subcutaneous Delivery of JNJ-54767414 (Daratumumab) in Japanese Participants With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2017-08-08
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the tolerability and safety of subcutaneous (SC) delivery of co-formulated daratumumab and rHuPH20 preparation (DARA SC) in Japanese participants with relapsed or refractory multiple myeloma (MM).


Eligibility criteria: Inclusion Criteria:

* Participant proven to have Multiple Myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria
* Participant must have measurable, secretory disease as defined by any of the following:

  1. Immunoglobulin (Ig) G MM: serum M-protein level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) or urine M-protein level \>= 200 milligram (mg)/24 hours; or
  2. IgA, IgD, IgE MM: serum M-protein level \>= 0.5 g/dL or urine M-protein level \>= 200 mg/24 hours; or
  3. Light chain MM, for participants without measurable disease in the serum or urine: serum Ig free light chains (FLC) \>= 10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
* Participant must have received \>= 2 prior lines of antimyeloma therapy without further established treatment option
* Participant must have relapsed or refractory disease
* Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
* The Participant must meet the following criteria of clinical laboratory test results during screening phase:

  1. hemoglobin \>=7.5 g/dL (\>=5 millimoles/liter \[mmol/L\]) (without prior Red Blood Cells (RBC) transfusion within 7 days before the laboratory test;
  2. absolute neutrophil count (ANC) \>=1.0\*10\^9/L (without granulocyte colony stimulating factor support in the 7 days prior the laboratory test);
  3. platelet count \>=75\*10\^9/L for participants in whom less than (\<)50.0 percent (%) of bone marrow nucleated cells are plasma cells; otherwise platelet count \>=50\*10\^9/L (without transfusion support in the 7 days prior to the laboratory test);
  4. aspartate aminotransferase (AST) less than or equal to (\<=)3.0 times upper limit of normal (ULN);
  5. alanine aminotransferase (ALT) \<=3.0 times ULN;
  6. creatinine clearance \>20 mL/minute/1.73 m\^2;
  7. total bilirubin \<=2.0 times ULN, except in participants with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin \<=1.5 times ULN is required);
  8. corrected serum calcium \<=14 mg/dL (\<=3.5 mmol/L)
* Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use highly effective methods of reliable birth control. Contraception must begin 4 weeks before initiating treatment, during therapy, during dose interruptions, and continue for 6 months following discontinuation of study therapy
* A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control, even if he had a successful vasectomy, for example, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 6 months after receiving the final dose of study drug

Exclusion Criteria:

* Participant has received daratumumab or other anti cluster of differentiation (CD)38 therapies previously
* Participant has received antimyeloma treatment within 2 weeks before Cycle 1 Day 1
* Participant has received autologous stem cell transplantation (ASCT) within 12 weeks before Cycle 1 Day 1, or the participant has previously received an allogenic stem cell transplant (regardless of timing)
* Participant has received a cumulative dose of corticosteroids equivalent or more than the equivalent of 140 mg of prednisolone within the 2-week period before Cycle 1 Day 1
* Participant has a history of malignancy (other than MM) within 3 years before Cycle 1 Day 1 (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)

Primary outcomes:
measure: Number of Participants With Adverse Events Including Dose Limiting Toxicity
timeFrame: Up to 30 days after last study drug dose (approximately up to 1 year)
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of Daratumumab
timeFrame: Up to 8 weeks after the last dose of study drug (approximately up to 1 year)
measure: Maximum Serum Trough Concentration (Ctrough) of Daratumumab
timeFrame: At Cycle 3 Day 1 predose concentration
measure: Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies
timeFrame: Up to 8 weeks after the last dose of study drug (approximately up to 1 year)
measure: Overall Response Rate
timeFrame: Approximately up to 1 year
measure: Duration of Response (DOR)
timeFrame: First documentation of confirmed PR or better to the date of first documented progressive disease (PD), or date of death due to PD, whichever occurs first (approximately up to 1 year)
measure: Time to Response
timeFrame: Approximately up to 1 year
Other outcomes:
Locations:
city: Gunma
country: Japan
facility: National Hospital Organization Shibukawa Medical Center
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Ohgaki
country: Japan
facility: Ogaki Municipal Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Shibuya
country: Japan
facility: Japanese Red Cross Medical Center
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Shibayama H, Matsumoto M, Kosugi H, Shibayama K, Yamazaki H, Iida S. Subcutaneous delivery of daratumumab in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2021 Jan;113(1):112-121. doi: 10.1007/s12185-020-02985-9. Epub 2020 Sep 11.