- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02492750
Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma
Phase I/II Double Blind Randomized Trial of Lenalidomide/Dexamethasone/Anakinra vs. Lenalidomide/Dexamethasone/Placebo in Patients With Early Stage Multiple Myeloma and High Plasma Cell Growth Rate
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD)/maximum allowable dose (MAD) of anakinra that can be combined with lenalidomide and dexamethasone. (Phase I) II. To compare the time to progression of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra). (Phase II)
SECONDARY OBJECTIVES:
I. To compare the response rate of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).
II. To compare the toxicity of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).
III. To compare the overall survival of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).
OUTLINE: This is a phase I, dose-escalation study of anakinra followed by a phase II study.
PHASE I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra subcutaneously (SC) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Absolute neutrophil count (ANC) >= 1700/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 8.0 g/dL
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x upper limit of normal (ULN)
- Creatinine clearance >= 30 mL/min (as determined by Cockroft-Gault equation)
Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:
- Smoldering multiple myeloma (SMM)
- Indolent multiple myeloma (IMM)
- Newly diagnosed multiple myeloma (MM)
- Note: patients with lytic disease and anemia are eligible
High risk disease defined by all of the following:
- >= 10% bone marrow plasma cells AND
- Abnormal serum free light chain (FLC) ratio (< 0.26 or > 1.65) by serum FLC assay AND
- Monotypic plasma cell S-phase >= 0.3%
- Measurable level of M-protein > 1 g/dL on serum protein electrophoresis or > 200 mg of M-protein on a 24 hour urine protein electrophoresis
- Negative tuberculosis (TB) testing (Quantiferon - TB blood test or skin test) =< 7 days prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
- Provide signed informed consent
- Negative (serum or urine) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: a second pregnancy test must be performed within 24 hours prior to the start of lenalidomide; the subject may not receive lenalidomide until the study doctor has verified that the results of these pregnancy tests are negative
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willing and able to comply with the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
- Females of childbearing potential must be willing to adhere to the scheduled pregnancy testing as required by the Revlimid REMS program
Exclusion Criteria:
- Prior treatment with any other agent that may affect M-protein =< 30 days prior to registration
- Acute/chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy =< 12 weeks prior to registration
- Other active malignancy (=< 3 years) prior to registration; exceptions: basal cell skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- New York Heart Association (NYHA) class 3 or 4 congestive heart failure (CHF) symptoms
- Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are allowed while on protocol treatment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Arm A (lenalidomide, dexamethasone, anakinra)
Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity
|
Correlative studies
Given PO
Other Names:
Given PO
Other Names:
Given SC
Other Names:
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ACTIVE_COMPARATOR: Arm B (lenalidomide, dexamethasone, placebo)
Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Correlative studies
Given PO
Other Names:
Given PO
Other Names:
Given SC
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
Time Frame: 28 days
|
Number of participants experiencing a dose-limiting toxicity (DLT) is reported below.
Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
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28 days
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Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0
Time Frame: Up to 41 months
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The number of participants who experienced at least one grade 3+ adverse events deemed at least possibly related to treatment, graded according to NCI CTCAE version 4.0, is reported below.
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Up to 41 months
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Best Response
Time Frame: Up to 41 months
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The following response terms will be used: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD).
The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy.
PR defined as: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24hrs; ≥ 50% reduction in the size of soft tissue plasmacytomas.
MR defined as: ≥25% but ≤ 49% reduction of serum M protein and reduction in 24-hour urine M-protein by 50-89% which still exceeds 200mg/24 hours; 25-49% reduction in the size of soft tissue plasmacytoma and No increase in the size or number of lytic bone lesions.
VGPR defined as: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h
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Up to 41 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: John Lust, Mayo Clinic
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Precancerous Conditions
- Hypergammaglobulinemia
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Smoldering Multiple Myeloma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Protease Inhibitors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dermatologic Agents
- Dexamethasone
- Dexamethasone acetate
- BB 1101
- Lenalidomide
- Interleukin 1 Receptor Antagonist Protein
- Ichthammol
Other Study ID Numbers
- MC138B (OTHER: Mayo Clinic)
- P30CA015083 (U.S. NIH Grant/Contract)
- NCI-2015-01041 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- RV-CL-MM-PI-004334
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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