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A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02316106
Recruitment Status : Active, not recruiting
First Posted : December 12, 2014
Last Update Posted : September 13, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate three daratumumab dose schedules in participants with Smoldering Multiple Myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: daratumumab Phase 2

Detailed Description:
This is a randomized, open-label (identity of assigned treatment will be known to participants and study staff), 3-arm (3 treatment groups), multicenter study of daratumumab in participants diagnosed with intermediate or high-risk Smoldering Multiple Myeloma (SMM [ie, early disease without any symptoms]). Participants will be randomized (assigned by chance) to one of 3 treatment groups (arm A [long intense], arm B [intermediate] and arm C [short intense]) to receive daratumumab. Each treatment group will investigate 1 of 3 dosing schedules of daratumumab. The study will include a 28-Day Screening Phase, a Treatment Phase of 1 to 20 treatment cycles (each cycle is 8 weeks in duration for total period of 8 to 160 weeks), and a Follow up Phase of 4-weeks from the last dose of study drug. For participants in Arm A (long intense) and Arm B (intermediate), there is a possibility to extend treatment with intravenous (IV) daratumumab (every 8 weeks [Q8W]) after the end of Cycle 20, as per investigator discretion. The Follow-up Phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. The end of the study will occur approximately 4 years after the last participant enrolled receives a first dose of study drug. Disease assessments will be performed every 8 weeks in the first year and then every 16 weeks until disease progression. Safety will be monitored throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Trial to Evaluate Three Daratumumab Dose Schedules in Smoldering Multiple Myeloma
Actual Study Start Date : May 20, 2015
Estimated Primary Completion Date : July 17, 2020
Estimated Study Completion Date : August 31, 2021

Resource links provided by the National Library of Medicine

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

Arm Intervention/treatment
Experimental: Arm A (Long Intense) Drug: daratumumab
16 mg/kg administered by intravenous (IV) infusion once every week in Cycle 1, every other week in Cycle 2 and Cycle 3, every 4 weeks in Cycle 4 to Cycle 7, and from Cycle 8 to Cycle 20 on Day 1 of each cycle, and every 8 weeks after Cycle 20, in case treatment will be extended as per investigator discretion, if there is a positive benefit/risk ratio, absence of Grade greater than or equal to (>=) 3 treatment related toxicity, and at least stable disease has been achieved. Treatment cycles are 8 weeks in length.

Experimental: Arm B (Intermediate) Drug: daratumumab
16 mg/kg administered by IV infusion once every week in Cycle 1, and then on Day 1 of each cycle from Cycle 2 to Cycle 20, and every 8 weeks after Cycle 20, in case treatment will be extended as per investigator discretion, if there is a positive benefit/risk ratio, absence of Grade >=3 treatment related toxicity, and at least stable disease has been achieved. Treatment cycles are 8 weeks in length.

Experimental: Arm C (Short Intense) Drug: daratumumab
16 mg/kg administered by IV infusion once every week in Cycle 1 only. Treatment cycles are 8 weeks in length.




Primary Outcome Measures :
  1. The percentage of participants who achieve a complete response (CR) [ Time Frame: Up to approximately 5 years ]
    CR, defined having negative immunofixation on the serum and urine, and <5% plasma cells (PCs) in bone marrow.

  2. The percentage of participants that have an event (disease progression or death) per patient-year [ Time Frame: Up to approximately 5.5 years ]

Secondary Outcome Measures :
  1. The percentage of participants who are minimal residual disease (MRD) negative [ Time Frame: Up to 5.5 years ]
  2. Time to next treatment (TNT) [ Time Frame: Up to 5.5 years ]
    TNT, defined as the time from the date of randomization to the date of the first subsequent multiple myeloma treatment.

  3. The percentage of participants who achieve a Complete Response (CR) or a Partial Response (PR) [ Time Frame: Up to 5.5 years ]
    See definition of CR above. PR, defined as >=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by >=90% or to <200 mg/24 hours.

  4. The median time of progression free survival (PFS) [ Time Frame: Up to 5.5 years ]
    PFS is defined as time from date of randomization to date of initial documented disease progression (PD) according to SLiM-CRAB (S=sixty, Li=light chains, M=MRI, C=calcium [elevated], R=renal failure, A=anemia, B=bone lesions) criteria, myeloma defining events, or date of death, whichever occurs first. As per SLiM-CRAB criteria, clonal bone marrow plasma cell percentage >=60%, Involved : uninvolved serum free Li ratio >= 100, >1 focal lesion on MRI studies, calcium elevation: >0.25 millimole per liter (mmol/L) ( >1 milligram per deciliter [mg/dL]) higher than upper limit of normal or >2.75 mmol/L (>11 mg/dL); creatinine clearance <40 milliliter per minute (mL/min) or serum creatinine >177 micromole per liter (µmol/L) (>2 mg/dL); hemoglobin <10 gram per deciliter (g/dL) (<6.5 mmol/L) or >2 g/dL (>1.25 mmol/L) lower than lower limit of normal; 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT).

  5. The percentage of participants with symptomatic multiple myeloma [ Time Frame: Up to 5.5 years ]
  6. Response to first subsequent multiple myeloma treatment [ Time Frame: Up to 5.5 years ]
  7. Overall survival rate [ Time Frame: Up to 5.5 years ]


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:

  • Diagnosis of smoldering multiple myeloma (SMM) for less than 5 years
  • Have a confirmed diagnosis of intermediate or high-risk SMM, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

  • Active multiple myeloma,requiring treatment as defined by the study protocol
  • Primary systemic AL (immunoglobulin light chain) amyloidosis
  • Prior or concurrent exposure to any of the following: approved or investigational treatments for SMM or/and multiple myeloma, daratumumab or other anti CD-38 therapies, treatment with corticosteroids with a dose greater than (>) 10 milligram (mg) prednisone per day or equivalent and bone-protecting agents (eg, bisphosphonates, denosumab) or are only allowed if given in a stable dose and for a nonmalignant condition, or received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before Cycle 1, Day 1
  • History of malignancy (other than SMM) within 3 years before the date of randomization, except for the following if treated and not active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, ductal carcinoma in situ of breast, or International Federation of Gynecology and Obstetrics (FIGO) Stage 1 carcinoma of the cervix
  • Known chronic obstructive pulmonary disease (COPD) OR moderate or severe persistent asthma within the past 2 years
  • Any concurrent medical or psychiatric condition or disease (eg, autoimmune disease, active systemic disease, myelodysplasia) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study

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): NCT02316106


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

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02316106     History of Changes
Other Study ID Numbers: CR106449
54767414SMM2001 ( Other Identifier: Janssen Research & Development, LLC )
2014-005139-14 ( EudraCT Number )
First Posted: December 12, 2014    Key Record Dates
Last Update Posted: September 13, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Janssen Research & Development, LLC:
Smoldering multiple myeloma (SMM)
Daratumumab
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Smoldering Multiple Myeloma
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
Precancerous Conditions
Hypergammaglobulinemia
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs