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A Study of Subcutaneous Versus (vs.) Intravenous Administration of Daratumumab in Participants With Relapsed or Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03277105
Recruitment Status : Recruiting
First Posted : September 8, 2017
Last Update Posted : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to show that subcutaneous (SC) administration of daratumumab co-formulated with recombinant human hyaluronidase PH20 (Dara SC) is non-inferior to intravenous (IV) administration of daratumumab (Dara IV) in terms of the overall response rate (ORR) and maximum trough concentration (Ctrough).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Dara SC Drug: Dara IV Phase 3

Detailed Description:
The study population will consist of adults diagnosed with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD. The study consists of 3 phases: a screening phase (up to 28 days), a treatment phase, and a follow-up phase. Efficacy, pharmacokinetics, immunogenicity, biomarkers and safety will be assessed at scheduled time. Follow-up will continue until the end of study, approximately 18 months after the last participant was randomized or when the sponsor decides to stop the study. The primary hypotheses is that the ORR and maximum Ctrough for Dara SC 1800 milligram (mg) are not inferior to the ORR and maximum Ctrough, respectively, for Dara IV 16 mg per kilogram (mg/kg) in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease is refractory to both a PI and an IMiD.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 480 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Multicenter Study of Subcutaneous vs. Intravenous Administration of Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : October 27, 2017
Estimated Primary Completion Date : November 5, 2019
Estimated Study Completion Date : October 8, 2020

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Dara SC
Participants will receive a fixed dose of daratumumab as 1800 milligram (mg) subcutaneously (Dara SC) co-formulated with recombinant human hyaluronidase (rHuPH20) 2000 Unit per milliliter (U/mL), once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study. The duration for each cycle is 4 weeks.
Drug: Dara SC
Participants will receive a fixed dose of Dara SC as 1800 mg daratumumab with rHuPH20 2000 U/mL, once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.

Active Comparator: Dara IV
Participants will receive daratumumab for intravenous infusion (Dara IV) 16 mg/kg by once weekly in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks at Day 1 in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
Drug: Dara IV
Participants will receive Dara IV 16 mg/kg once weekly at in Cycle 1 and 2, every 2 weeks in Cycle 3 to 6, every 4 weeks in Cycle 7 and thereafter until disease progression, unacceptable toxicity or the end of study.
Other Name: JNJ-54767414




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) ]
    The ORR is defined as the proportion of participants who achieve partial response (PR) or better according to international myeloma working group (IMWG) criteria, during or after study treatment. IMWG criteria for PR: greater than or equal to (>=) 50 percent (%) reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to lesss than (<) 200 mg/24 hours, If the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved free light chain (FLC) levels is required in place of the Mprotein criteria, If serum and urine M-protein are not measurable, and serum free light assay is also not measurable, >=50% reduction in bone marrow plasma cells (PCs) is required in place of M-protein, provided baseline bone marrow plasma cell percentage was >=30%. In addition to the above criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required.

  2. Maximum Trough Concentration (Ctrough) of Daratumumab [ Time Frame: Cycle 3 (each cycle 28 days) Day 1 ]
    Maximum Ctrough is defined as the serum predose concentration of daratumumab on Cycle 3 Day 1.


Secondary Outcome Measures :
  1. Percentage of participants With Infusion-Related Reactions (IRR) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) ]
    The Percentage of Participants with infusion reactions will be reported.

  2. Progression-Free Survival (PFS) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    PFS is defined as time from date of randomization to either progression of disease (PD), death due to any cause, whichever occurs first. According to IMWG criteria: Increase of 25% from lowest response value in any one of the following: Serum M component (absolute increase must be >=0.5 gram per deciliter (g/dL), Urine M-component (absolute increase must be >=200 mg/24 hours), Participants without measurable serum and urine Mprotein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase must be >10 milligrams per deciliter (mg/dL), participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow PC% (absolute percentage must be >=10%), definite development of new bone lesions or soft tissue plasmacytomas or increase in size of bone lesions or tissue plasmacytomas and development of hypercalcemia (serum calcium >11.5 mg/dL) that can be attributed solely to PC proliferative disorder.

  3. Very Good Partial Response (VGPR) or Better Rate [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    The VGPR or better rate, defined as the proportion of participants achieving VGPR and complete response (CR) (including stringent complete response [sCR]) according IMWG criteria during or after the study treatment. IMWG criteria for VGPR: Serum and urine M-component detectable by immunofixation but not on electrophoresis, or greater than equal to (>=) 90 percent (%) reduction in serum M-protein plus urine M-protein <100 milligram (mg)/24 hours, CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas and <5% plasma cellS (PCs) in bone marrow. sCR: CR plus normal free light chain (FLC) ratio, and absence of clonal PCs by immunohistochemistry (IHC), immunofluorescencea or 2- to 4 color flow cytometry.

  4. Complete Response (Including sCR) or Better Rate [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Complete response is based on serum M-Protein assessments. IMWG criteria for CR: Negative immunofixation on the serum and urine, and disappearance of any soft tissue plasmacytomas, and <5% PCs in bone marrow. sCR: CR plus normal FLC ratio, and absence of clonal PCs by IHC, immunofluorescencea or 2- to 4 color flow cytometry.

  5. Time to Next Treatment [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Time to next therapy is defined as the time from randomization to the start of the first subsequent anti-cancer therapy.

  6. Overall Survival (OS) [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    OS is defined as the time from the date of randomization to the date of the participant's death.

  7. Patient-Reported Satisfaction With Therapy [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Patient-reported satisfaction with therapy is defined as the mean of responses to 7 of 9 questions in the modified cancer therapy satisfaction questionnaire (modified-CTSQ). Modified-CTSQ contain 9 items specific to satisfaction with therapy and for comparison of IV with SC administration. Satisfaction with therapy is calculated based on 7-items using 5-point verbal rating scale, 1, never; 5, always. Scores will be averaged and transformed to a 0-100 scale; higher scores represent better health.

  8. Duration of Response [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Duration of response is defined as date of onset of first response until date of disease progression or death.

  9. Time to response [ Time Frame: At 6 months after last participant randomized (approximately 2 years) and 18 months after the last participant randomized (approximately 3 years) ]
    Time to response is defined as the time from randomization until onset of first response.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the course of treatment (except for participants who discontinued either of these treatments due to a severe allergic reaction within the first 2 cycles/months). A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy. Radiotherapy, bisphosphonate, or a single short course of corticosteroids (no more than the equivalent of dexamethasone 40 milligram/day [mg/day] for 4 days) would not be considered prior lines of therapy
  • Documented multiple myeloma as defined by the criteria below:

    1. Multiple myeloma diagnosis according to the IMWG diagnostic criteria
    2. Measurable disease at Screening as defined by any of the following:

      1. Serum M-protein level >=1.0 gram per deciliter (g/dL) or urine M-protein level >=200 mg/24 hours; or
      2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Meet the clinical laboratory criteria as specified in the protocol
  • Women of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization

Exclusion Criteria:

  • Received daratumumab or other anti-CD38 therapies previously
  • Received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum of 4 days before treatment
  • Received autologous stem cell transplant within 12 weeks before the date of randomization, or the participant has previously received allogeneic stem cell transplant (regardless of timing)
  • 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) if all treatment of that malignancy was completed at least 2 years before consent and the patient has no evidence of disease (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or breast, or other non-invasive lesion, 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)

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): NCT03277105


Contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

  Show 166 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03277105     History of Changes
Other Study ID Numbers: CR108342
2017-000206-38 ( EudraCT Number )
54767414MMY3012 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs