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

Primary Purpose

Multiple Myeloma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Daratumumab Subcutaneous (SC) Administration

Recombinant Human Hyaluronidase [rHuPH20]) SC Administration

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Daratumumab (JNJ-54767414), Recombinant Human Hyaluronidase

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Part 1: Cohort 1

Part 1: Cohort 2

Part 1: Cohort 3

Part 2: Cohort 4

Part 3: Dara-CF 1800 mg

Arm Description

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Serum Trough Concentrations (Ctrough) of Daratumumab

Ctrough: the concentration prior to study drug administration.

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.

Secondary Outcome Measures

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

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)

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)

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)

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 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)

Full Information

NCT ID

NCT02519452

First Posted

August 6, 2015

Last Updated

May 4, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02519452

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Completed

Study Start Date

October 2015 (Actual)

Primary Completion Date

December 2017 (Actual)

Study Completion Date

September 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Cohort 1

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Cohort 2

Arm Type

Experimental

Arm Description

Arm Title

Part 1: Cohort 3

Arm Type

Experimental

Arm Description

Arm Title

Part 2: Cohort 4

Arm Type

Experimental

Arm Description

Arm Title

Part 3: Dara-CF 1800 mg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Daratumumab Subcutaneous (SC) Administration

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Recombinant Human Hyaluronidase [rHuPH20]) SC Administration

Intervention Description

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.

Primary Outcome Measure Information:

Title

Serum Trough Concentrations (Ctrough) of Daratumumab

Description

Ctrough: the concentration prior to study drug administration.

Time Frame

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

Title

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

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

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

Description

Serum levels of antibodies to Daratumumab and rHuPH20 for evaluation of potential immunogenicity.

Time Frame

Approximately 2 years

Title

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

Description

CR is Defined as the proportion of Participants achieving CR (including sCR) according to the International Myeloma Working Group (IMWG) criteria.

Time Frame

Approximately 2 years

Title

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

Description

Time Frame

Approximately 2 years

Title

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

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.

Time Frame

Approximately 2 years

Title

Part 1, 2 and 3: Time to Response

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)

Time Frame

Approximately 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Atlanta

State/Province

Georgia

Country

United States

City

New York

State/Province

New York

Country

United States

City

Charlotte

State/Province

North Carolina

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Vejle

Country

Denmark

City

Nantes Cedex 1

Country

France

City

Tours cedex

Country

France

City

Amsterdam

Country

Netherlands

City

Badalona

Country

Spain

City

Pamplona

Country

Spain

City

Salamanca

Country

Spain

City

Stockholm

Country

Sweden

12. IPD Sharing Statement

Citations:

PubMed Identifier

31270103

Citation

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.

Results Reference

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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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