A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma
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ClinicalTrials.gov Identifier: NCT02519452 |
Recruitment Status :
Active, not recruiting
First Posted : August 11, 2015
Last Update Posted : December 4, 2020
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Condition or disease | Intervention/treatment | Phase |
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Multiple Myeloma | Drug: Daratumumab Subcutaneous (SC) Administration Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 120 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | October 22, 2015 |
Actual Primary Completion Date : | December 13, 2017 |
Estimated Study Completion Date : | November 30, 2022 |

Arm | Intervention/treatment |
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Experimental: Part 1: Cohort 1
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.
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Drug: Daratumumab Subcutaneous (SC) Administration
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration Participants will receive Recombinant Human Hyaluronidase [rHuPH20]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. |
Experimental: Part 1: Cohort 2
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.
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Drug: Daratumumab Subcutaneous (SC) Administration
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration Participants will receive Recombinant Human Hyaluronidase [rHuPH20]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. |
Experimental: Part 1: Cohort 3
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.
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Drug: Daratumumab Subcutaneous (SC) Administration
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration Participants will receive Recombinant Human Hyaluronidase [rHuPH20]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. |
Experimental: Part 2: Cohort 4
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.
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Drug: Daratumumab Subcutaneous (SC) Administration
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration Participants will receive Recombinant Human Hyaluronidase [rHuPH20]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. |
Experimental: Part 3: Dara-CF 1800 mg
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.
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Drug: Daratumumab Subcutaneous (SC) Administration
Participants will receive Daratumumab mixed with rHuPH20 in part 1 and co-formulated with rHuPH20 in part 2 and part 3 administered via SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration Participants will receive Recombinant Human Hyaluronidase [rHuPH20]) mixed with Daratumumab in part 1 and co-formulated with Daratumumab in part 2 and part 3 administered as SC administration once weekly in Cycles 1 (each cycle is 28 days) and 2, every 2 weeks in Cycles 3-6, and every 4 weeks in subsequent cycles. |
- Serum Trough Concentrations (Ctrough) of Daratumumab [ Time Frame: Up to cycle 3 (each cycle 28 days) Day 1 ]Ctrough: the concentration prior to study drug administration.
- Part 1, 2 and 3: Number of Participants with Adverse Events (AEs) and Serious AEs [ Time Frame: Screening up to follow-up (30 days after last dose administration) (Approximately up to 3.4 years) ]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.
- Part 1, 2 and 3: Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies [ Time Frame: Approximately 2 years ]Serum levels of antibodies to Daratumumab and rHuPH20 for evaluation of potential immunogenicity.
- Part 1, 2 and 3: Percentage of Participants with Complete Response (CR) [ Time Frame: Approximately 2 years ]CR is Defined as the proportion of Participants achieving CR (including sCR) according to the International Myeloma Working Group (IMWG) criteria.
- Part 1, 2 and 3: Percentage of Participants With Overall Response Rate (ORR) [ Time Frame: Approximately 2 years ]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.
- Part 1, 2 and 3: Duration of Response (DR) [ Time Frame: Approximately 2 years ]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.
- Part 1, 2 and 3: Time to Response [ Time Frame: Approximately 2 years ]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)

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02519452
United States, Georgia | |
Atlanta, Georgia, United States | |
United States, New York | |
New York, New York, United States | |
United States, North Carolina | |
Charlotte, North Carolina, United States | |
United States, Pennsylvania | |
Philadelphia, Pennsylvania, United States | |
Denmark | |
Vejle, Denmark | |
France | |
Nantes Cedex 1, France | |
Tours cedex, France | |
Netherlands | |
Amsterdam, Netherlands | |
Spain | |
Badalona, Spain | |
Pamplona, Spain | |
Salamanca, Spain | |
Sweden | |
Stockholm, Sweden |
Study Director: | Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC |
Responsible Party: | Janssen Research & Development, LLC |
ClinicalTrials.gov Identifier: | NCT02519452 |
Other Study ID Numbers: |
CR107838 2015-001210-94 ( EudraCT Number ) 54767414MMY1004 ( Other Identifier: Janssen Research & Development, LLC ) |
First Posted: | August 11, 2015 Key Record Dates |
Last Update Posted: | December 4, 2020 |
Last Verified: | December 2020 |
Studies a U.S. FDA-regulated Device Product: | No |
Multiple Myeloma Daratumumab (JNJ-54767414) Recombinant Human Hyaluronidase |
Multiple Myeloma Daratumumab Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Antineoplastic Agents |