A Study of Daratumumab With the Addition of Recombinant Human Hyaluronidase (rHuPH20) for the Treatment of Participants With Relapsed or Refractory Multiple Myeloma

NCT02519452 | Completed Phase 1

• 3 other identifiers: CR1078382015-001210-9454767414MMY1004
• Study Type: interventional
• Target: 120
• Locations: 6 countries
• Sites: 12

Brief Summary

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).

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Daratumumab (JNJ-54767414); Recombinant Human Hyaluronidase

Outcome Measures

Primary Outcomes (2)

• Serum Trough Concentrations (Ctrough) of Daratumumab

  Ctrough: the concentration prior to study drug administration.

  Up to cycle 3 (each cycle 28 days) Day 1

• Part 1, 2 and 3: Number of Participants with Adverse Events (AEs) and Serious AEs

  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.

  Screening up to follow-up (30 days after last dose administration) (Approximately up to 3.4 years)

Secondary Outcomes (5)

• Part 1, 2 and 3: Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies

  Approximately 2 years

• Part 1, 2 and 3: Percentage of Participants with Complete Response (CR)

  Approximately 2 years

• Part 1, 2 and 3: Percentage of Participants With Overall Response Rate (ORR)

  Approximately 2 years

• Part 1, 2 and 3: Duration of Response (DR)

  Approximately 2 years

• Part 1, 2 and 3: Time to Response

  Approximately 2 years

Study Arms (5)

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.

Drug: Daratumumab Subcutaneous (SC) Administration; Drug: 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.

Drug: Daratumumab Subcutaneous (SC) Administration; Drug: 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.

Drug: Daratumumab Subcutaneous (SC) Administration; Drug: 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.

Drug: Daratumumab Subcutaneous (SC) Administration; Drug: 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.

Drug: Daratumumab Subcutaneous (SC) Administration; Drug: Recombinant Human Hyaluronidase [rHuPH20]) SC Administration

Interventions

Daratumumab Subcutaneous (SC) Administration DRUG

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.

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Cohort 3; Part 2: Cohort 4; Part 3: Dara-CF 1800 mg

Recombinant Human Hyaluronidase [rHuPH20]) SC Administration DRUG

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.

Part 1: Cohort 1; Part 1: Cohort 2; Part 1: Cohort 3; Part 2: Cohort 4; Part 3: Dara-CF 1800 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (12)

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

New York, New York, United States

Location

Unknown Facility

Charlotte, North Carolina, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, United States

Location

Unknown Facility

Vejle, Denmark

Location

Unknown Facility

Nantes, France

Location

Unknown Facility

Tours, France

Location

Unknown Facility

Amsterdam, Netherlands

Location

Unknown Facility

Badalona, Spain

Location

Unknown Facility

Pamplona, Spain

Location

Unknown Facility

Salamanca, Spain

Location

Unknown Facility

Stockholm, Sweden

Location

Related Publications (3)

• Li X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6.

  PMID: 37022569 DERIVED

• Nahi H, Usmani SZ, Mateos MV, van de Donk NWCJ, Oriol A, Plesner T, Bandyopadhyay N, Hellemans P, Tromp B, Nnane I, Zemlickis D, Chari A, Moreau P. Corticosteroid tapering is a safe approach in patients with relapsed or refractory multiple myeloma receiving subcutaneous daratumumab: part 3 of the open-label, multicenter, phase 1b PAVO study. Leuk Lymphoma. 2023 Feb;64(2):468-472. doi: 10.1080/10428194.2022.2148221. Epub 2023 Jan 2. No abstract available.

  PMID: 36593729 DERIVED

• Usmani SZ, Nahi H, Mateos MV, van de Donk NWCJ, Chari A, Kaufman JL, Moreau P, Oriol A, Plesner T, Benboubker L, Hellemans P, Masterson T, Clemens PL, Luo M, Liu K, San-Miguel J. Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. Blood. 2019 Aug 22;134(8):668-677. doi: 10.1182/blood.2019000667. Epub 2019 Jul 3.

  PMID: 31270103 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Organization and Administration

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Health Services Administration

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 11, 2015
• Study Start: October 22, 2015
• Primary Completion: December 13, 2017
• Study Completion: April 3, 2023
• Last Updated: May 23, 2025

Record last verified: 2025-05

Locations

DK (1); FR (2); US (4); NL (1); ES (3); SE (1)