Description:
The purpose of the study is to evaluate the pharmacokinetics and safety from the mixture of
daratumumab and rHuPH20 prepared immediately before administration via Subcutaneous (SC)
delivery (Part 1) and CF (co-formulated daratumumab and rHuPH20 preparation) administration
via SC delivery of daratumumab (Part 2) and to evaluate the safety of Dara-CF 1800 milligram
(mg) SC delivery without pre-dose and post-dose corticosteroids (Part 3).
Title
- Brief Title: A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
- Official Title: An Open-label, Multicenter, Dose Escalation Phase 1b Study to Assess the Safety and Pharmacokinetics of Subcutaneous Delivery of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Subjects With Relapsed or Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
CR107838
- SECONDARY ID:
2015-001210-94
- SECONDARY ID:
54767414MMY1004
- NCT ID:
NCT02519452
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Daratumumab Subcutaneous (SC) Administration | | Part 1: Cohort 1 |
| Recombinant Human Hyaluronidase [rHuPH20]) SC Administration | | Part 1: Cohort 1 |
Purpose
The purpose of the study is to evaluate the pharmacokinetics and safety from the mixture of
daratumumab and rHuPH20 prepared immediately before administration via Subcutaneous (SC)
delivery (Part 1) and CF (co-formulated daratumumab and rHuPH20 preparation) administration
via SC delivery of daratumumab (Part 2) and to evaluate the safety of Dara-CF 1800 milligram
(mg) SC delivery without pre-dose and post-dose corticosteroids (Part 3).
Detailed Description
This is an open-label (identity of assigned study drug will be known), multicenter, 3-part,
Phase 1b dose escalation/expansion study to evaluate the safety, pharmacokinetics (study of
what the body does to a drug), and antitumor activity of SC delivery of daratumumab to
participant with relapsed or refractory multiple myeloma. Up to approximately 53 participants
in part 1, 80 participants in part 2 and 15 participants per corticosteroid tapering cohort
(up to approximately 30 participants total) in Part 3 will be enrolled. The purpose of Part 1
is to select an appropriate SC therapeutic dose for the mixture of daratumumab with rHuPH20
based on safety and pharmacokinetics. This dose, selected from part 1 will be the initial
dose for the co-formulated daratumumab and rHuPH20 preparation to be evaluated in Part 2. The
purpose of Part 2 is to evaluate the SC delivery of CF and confirm the dose level selected
from Part 1 based on the pharmacokinetics, safety, and antitumor activity. The purpose of
Part 3 is to evaluate the safety of Dara-CF 1800 mg SC delivery without pre-dose and
post-dose corticosteroids. Participant's safety will be monitored throughout the study.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Part 1: Cohort 1 | Experimental | Participants will receive 1200 mg (daratumumab 1200 milligram (mg) with Recombinant Human Hyaluronidase [rHuPH20] 30,000 U) via mixing immediately before Subcutaneous (SC) infusion once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and then every 4 weeks in subsequent cycles until disease progression. | - Daratumumab Subcutaneous (SC) Administration
- Recombinant Human Hyaluronidase [rHuPH20]) SC Administration
|
| Part 1: Cohort 2 | Experimental | Participants will receive 1800 mg (daratumumab 1800 milligram (mg) with Recombinant Human Hyaluronidase [rHuPH20] 45,000 U) via mixing immediately before SC infusion once weekly in Cycles 1 and 2, every 2 weeks in Cycles 3-6, and then every 4 weeks in subsequent cycles until disease progression. | - Daratumumab Subcutaneous (SC) Administration
- Recombinant Human Hyaluronidase [rHuPH20]) SC Administration
|
| Part 1: Cohort 3 | Experimental | Participants will receive mixture of daratumumab and rHuPH20 prepared immediately before administration via Subcutaneous (SC) delivery at a dose which will be decided by Study Evaluation Team (SET) once weekly by SC infusion in Cycles 1 and 2, every 2 weeks in Cycles 3-6, and then every 4 weeks in subsequent cycles until disease progression. Also up to three additional optional cohorts (Cohorts 3b, 3c, and 3d) may be enrolled to repeat a dose level of daratumumab. | - Daratumumab Subcutaneous (SC) Administration
- Recombinant Human Hyaluronidase [rHuPH20]) SC Administration
|
| Part 2: Cohort 4 | Experimental | Participants will receive 1800 mg co-formulated daratumumab and rHuPH20 preparation initially administered by SC injection once weekly in Cycles 1 and 2, every 2 weeks in Cycles 3-6, and then every 4 weeks in subsequent cycles. The dose level and schedule for any additional cohorts would be selected based on the daratumumab pharmacokinetic profile and safety profile (reviewed by the SET) that will be observed in Cohort 4. | - Daratumumab Subcutaneous (SC) Administration
- Recombinant Human Hyaluronidase [rHuPH20]) SC Administration
|
| Part 3: Dara-CF 1800 mg | Experimental | Participants will receive co-formulated daratumumab 1800 mg and rHuPH20 preparation (Dara-CF) initially administered by SC injection once weekly in Cycles 1 and 2, every 2 weeks in Cycles 3-6, and then every 4 weeks in subsequent cycles. | - Daratumumab Subcutaneous (SC) Administration
- Recombinant Human Hyaluronidase [rHuPH20]) SC Administration
|
Eligibility Criteria
Inclusion Criteria:
- Participants proven to have multiple myeloma (MM) diagnosis according to the
International Myeloma Working Group (IMWG) diagnostic criteria
- Measurable disease as defined by any of the following: (a) immunoglobulin (Ig) G
myeloma (serum monoclonal paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or
urine M-protein level greater than or equal to (>=) 200 milligram[mg]/24 hours[hrs];
or (b) IgA, IgD, or IgE multiple myeloma (serum M-protein level >= 0.5 g/dL or urine
M-protein level >= 200 mg/24 hrs); or (c) light chain multiple myeloma (serum
immunoglobulin free light chain >=10 mg/dL and abnormal serum immunoglobulin kappa
lambda free light chain ratio)
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0, 1, or 2
- Pretreatment clinical laboratory values must meet protocol-defined parameters during
the Screening phase
- Man, who is sexually active with a woman of child-bearing potential and has not had a
vasectomy, must agree to use a barrier method of birth control example (eg), 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 3 months after
receiving the final dose of study drug
- Relapsed or refractory disease. Relapse is defined as progression of disease after an
initial response to previous treatment, more than 60 days after cessation of
treatment. Refractory disease is defined as less than (<) 25 percent (%) reduction in
M-protein or progression of disease during treatment or within 60 days after cessation
of treatment
- Prior treatment with less than or equal to (>=) 2 treatment lines of anti-myeloma
therapy. Prior lines of therapy must include a proteasome inhibitor (PI) (eg,
bortezomib, carfilzomib) and an immunomodulatory drug (IMiD) (example, thalidomide,
lenalidomide, pomalidomide) in any order during the course of treatment. Each prior
line of therapy may consist of one or more agents and may include induction,
hematopoietic stem cell transplantation, and/or maintenance therapy. Radiotherapy,
bisphosphonates, or a single short course of steroids is not considered a prior line
of therapy
Exclusion Criteria:
- Participant has received daratumumab or other anti-cluster of differentiation 38
(anti-CD38) therapies previously
- Participant has received anti-myeloma treatment within 2 weeks before Cycle 1 Day 1
- Participant has previously received an allogenic stem cell transplant; or participant
has received autologous stem cell transplantation (ASCT) within 12 weeks before Cycle
1 Day 1
- Participant has a history of malignancy (other than multiple myeloma) within 5 years
before Cycle 1 Day 1 (exceptions are squamous and basal cell carcinomas of the skin
and carcinoma in situ of the cervix, 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)
- Participant is exhibiting clinical signs of meningeal involvement of multiple myeloma
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Serum Trough Concentrations (Ctrough) of Daratumumab |
| Time Frame: | Up to cycle 3 (each cycle 28 days) Day 1 |
| Safety Issue: | |
| Description: | Ctrough: the concentration prior to study drug administration. |
Secondary Outcome Measures
| Measure: | Part 1, 2 and 3: Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Serum levels of antibodies to Daratumumab and rHuPH20 for evaluation of potential immunogenicity. |
| Measure: | Part 1, 2 and 3: Percentage of Participants with Complete Response (CR) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | CR is Defined as the proportion of Participants achieving CR (including sCR) according to the International Myeloma Working Group (IMWG) criteria. |
| Measure: | Part 1, 2 and 3: Percentage of Participants With Overall Response Rate (ORR) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Overall response rate is defined as the percentage of participants who achieve complete response, stringent complete response (sCR), partial response or very good partial response (VGPR) according to the International Myeloma Working Group criteria, during or after study treatment. |
| Measure: | Part 1, 2 and 3: Duration of Response (DR) |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | The DR is time from date of initial documentation of response (PR or better) to date of first documented PD, as defined by IMWG criteria. |
| Measure: | Part 1, 2 and 3: Time to Response |
| Time Frame: | Approximately 2 years |
| Safety Issue: | |
| Description: | Time to response is defined as the time from the date of first dose of study treatment to the date of the first documentation of observed response (CR or PR or better than PR) |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Janssen Research & Development, LLC |
Trial Keywords
- Multiple Myeloma
- Daratumumab (JNJ-54767414)
- Recombinant Human Hyaluronidase
Last Updated
December 4, 2020
