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A Study of JNJ-63723283, an Anti-programmed Death-1 Monoclonal Antibody, Administered in Combination With Daratumumab, Compared With Daratumumab Alone in Participants With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03357952
Recruitment Status : Active, not recruiting
First Posted : November 30, 2017
Last Update Posted : December 4, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The main purpose of this study is to assess the safety of the combination of JNJ-63723283 and daratumumab (Part 1); to compare the overall response rate (ORR) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 2); and to compare progression-free survival (PFS) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 3).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: JNJ-63723283 Phase 2 Phase 3

Detailed Description:
This is a multi-phase study of JNJ-63723283 in combination with daratumumab compared with daratumumab alone in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or whose disease is double refractory to both a PI and an IMiD. The study consists of Screening Phase (procedures performed within 28 days before enrollment), Open-Label Treatment Phase (with End-of-Treatment Visit to occur 4 weeks after the last dose of study treatment) and Follow-up phase (8 weeks after the last dose of study treatment). Ongoing safety evaluation during Part 1 and Part 2 will be overseen by the Safety Evaluation Team (SET). In Part 3, ongoing safety and efficacy evaluation will be performed by the Independent Data Monitoring Committee (IDMC).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, Administered in Combination With Daratumumab, Compared With Daratumumab Alone in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : November 16, 2017
Actual Primary Completion Date : October 24, 2018
Estimated Study Completion Date : December 15, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: Part 1: JNJ‑63723283 + Daratumumab
Participants in Safety Run-in cohort will receive daratumumab IV and JNJ‑63723283 IV for 1 cycle (28 days). Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
Drug: Daratumumab
Participants will receive daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) once every week for 8 weeks (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards).
Other Name: JNJ-54767414

Drug: JNJ-63723283
Participants will receive JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.

Experimental: Part 2 and Part 3: Daratumumab/ JNJ‑63723283 + Daratumumab
Participants in Treatment Arm A will receive daratumumab IV and in Treatment Arm B will receive daratumumab IV and JNJ‑63723283 IV for cycles of 28 days each. All participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met.
Drug: Daratumumab
Participants will receive daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) once every week for 8 weeks (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards).
Other Name: JNJ-54767414

Drug: JNJ-63723283
Participants will receive JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.




Primary Outcome Measures :
  1. Part 1: Number of Participants With Adverse Event Including Dose-Limiting Toxicities (DLTs) [ Time Frame: From signing informed consent form (ICF) until 30 days after last study treatment dose (approximately up to 2 years) ]
    An adverse event (AE) is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. The DLT observation period for Part 1 is 28 days in Cycle 1.

  2. Part 2: Overall Response Rate (ORR) [ Time Frame: Approximately up to 11 months ]
    Overall Response is partial response (PR)/better as per International Myeloma Working Group (IMWG) criteria.

  3. Part 3: Progression-Free Survival (PFS) [ Time Frame: Approximately up to 18 months ]
    PFS is defined as the time from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.


Secondary Outcome Measures :
  1. Part 2 and Part 3: Number of Participants With Averse Events (AEs) Including Immune-related AEs and Infusion-related Reactions [ Time Frame: From signing ICF until 30 days after last study treatment dose (approximately up to 2 years) ]
    Number of participants with adverse events, including immune-related AEs and infusion-related reactions will be assessed.

  2. Part 2 and Part 3: Percentage of Participants With a Very Good Partial Response (VGPR) or Better [ Time Frame: For Part 2: approximately up to 11 months, Part 3: approximately up to 18 months ]
    VGPR or better rate defined as the percentage of participants with a best response of at least VGPR, as per the the IMWG criteria during or after the study treatment.

  3. Part 2 and Part 3: Percentage of Participants With Complete Response (CR) or Better [ Time Frame: For Part 2: approximately up to 11 months, Part 3: approximately up to 18 months ]
    CR or better rate defined as the percentage of participants with a best response of at least CR, as per the IMWG criteria during or after the study treatment.

  4. Part 2 and Part 3: Duration of Response (DOR) [ Time Frame: For Part 2: approximately up to 11 months, Part 3: approximately up to 18 months ]
    Duration of response is defined as the time from onset of first response until date of disease progression or death.

  5. Part 2 and Part 3: Time to Response [ Time Frame: For Part 2: approximately up to 11 months, Part 3: approximately up to 18 months ]
    Time to response is defined as the time between the date of randomization and the onset of first response.

  6. Part 2: Progression Free Survival (PFS) [ Time Frame: For Part 2: approximately up to 11 months ]
    PFS is defined as the time from the date of randomization to the date of disease progression or death due to any cause, whichever occurs first.

  7. Part 2 and Part 3: Overall Survival (OS) [ Time Frame: From the date of randomization to the date of death (approximately up to 2 years) ]
    OS is defined as the time from the date of randomization to the date of death.

  8. Part 2 and Part 3: Minimal Residual Disease (MRD) Negative Rate [ Time Frame: Approximately up to 2 years ]
    MRD-negative rate is defined as the percentage of MRD- negative participants compared to the number of participants randomized in the study.

  9. Part 2 and Part 3: Serum Concentrations of JNJ-63723283 [ Time Frame: Approximately up to 2 years ]
    Concentration assessment will be done to evaluate the exposure of JNJ-63723283.

  10. Part 2 and Part 3: Serum Concentrations of Daratumumab [ Time Frame: Approximately up to 2 years ]
    Concentration assessment will be done to evaluate the exposure of daratumumab.

  11. Part 2 and Part 3: Number of Participants With Anti-JNJ-63723283 Antibodies [ Time Frame: Approximately up to 2 years ]
    Number of participants with anti-JNJ-63723283 antibodies will be reported.

  12. Part 2 and Part 3: Number of Participants With Anti-daratumumab Antibodies [ Time Frame: Approximately up to 2 years ]
    Number of participants with anti-daratumumab antibodies will be reported.

  13. Part 3: Overall Response Rate (ORR) [ Time Frame: Approximately up to 18 months ]
    Overall Response is partial response (PR)/better as per International Myeloma Working Group (IMWG) criteria.

  14. Part 3: Change From Baseline in Disease-Related Symptom Scales of the EORTC QLQ-C30 [ Time Frame: Baseline, Day 1 of every 3rd cycle (Cycles 3, 6, 9, 12) until progressive disease (PD) (approximately up to 2 years) ]
    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher score equal to (=) better level of functioning or greater degree of symptoms.

  15. Part 3: Change From Baseline in Functioning Scale of the EORTC QLQ-C30 [ Time Frame: Baseline, Day 1 of every 3rd cycle (Cycles 3, 6, 9, 12) until progressive disease (PD) (approximately up to 2 years) ]
    EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher score=better level of functioning or greater degree of symptoms.

  16. Part 3: Change From Baseline in Global Health Status (GHS) Scale of the EORTC QLQ-C30 [ Time Frame: Baseline, Day 1 of every 3rd cycle (Cycles 3, 6, 9, 12) until progressive disease (PD) (approximately up to 2 years) ]
    EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 Global Health Status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Scores are transformed to a 0 to 100 scale. Higher score=better level of functioning or greater degree of symptoms.

  17. Part 3: Change From Baseline in the Visual Analog Scale (VAS) of the EQ-5D-5L [ Time Frame: Baseline, Day 1 of every 3rd cycle (Cycles 3, 6, 9, 12) until PD (approximately up to 2 years) ]
    The European Quality of Life 5 Dimensions Questionnaire (EQ-5D-5L) is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).

  18. Part 3: Change From Baseline in the Utility Scale of the EQ-5D-5L [ Time Frame: Baseline, Day 1 of every 3rd cycle (Cycles 3, 6, 9, 12) until PD (approximately up to 2 years) ]
    The EQ-5D-5L will be used to generate utility scores for use in cost effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression.



Information from the National Library of Medicine

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
Criteria

Inclusion Criteria:

  • Have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) in any order during the course of treatment for multiple myeloma or have disease that is refractory to both a PI and an IMiD
  • Evidence of a response (partial response [PR] or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to at least 1 prior treatment regimen
  • Documented measurable disease for multiple myeloma at screening as defined in protocol
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion Criteria:

  • Received any of the following prescribed medications or therapies in the past: Anti-CD38 antibody, including daratumumab, and/or Anti-PD-1 (programmed death-1) and anti-PD-L1 (programmed death-ligand 1) antibodies
  • Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)
  • History of malignancy (other than multiple myeloma) within 2 years prior to first administration of study drug (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 within 3 years)
  • Clinical signs of meningeal involvement of multiple myeloma
  • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal or known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification

Information from the National Library of Medicine

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): NCT03357952


Locations
Belgium
ZNA Stuivenberg
Antwerpen, Belgium, 2060
Algemeen Ziekenhuis Klina
Brasschaat, Belgium, 2930
AZ St.-Jan Brugge-Oostende AV
Brugge, Belgium, 8000
UZBrussel
Brussel, Belgium, 1090
UZA
Edegem, Belgium, 2650
UZ Gent
Gent, Belgium, 9000
Az Groeninge
Kortrijk, Belgium, 8500
Israel
Rambam Medical Center
Haifa, Israel, 31096
Carmel Hospital
Haifa, Israel, 34362
Hadassah Medical Center
Jerusalem, Israel, 91120
Sourasky Medical Center
Tel-Aviv, Israel, 6423906
Spain
Hosp. Univ. Germans Trias I Pujol
Badalona, Spain, 08916
Clinica Univ. de Navarra
Pamplona, Spain, 31008
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03357952     History of Changes
Other Study ID Numbers: CR108381
2017-002611-34 ( EudraCT Number )
54767414MMY2036 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: November 30, 2017    Key Record Dates
Last Update Posted: December 4, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
Multiple Myeloma
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
Antibodies
Antibodies, Monoclonal
Daratumumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents