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Trial record 85 of 371 for:    LENALIDOMIDE AND Dexamethasone

Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT02492750
Recruitment Status : Completed
First Posted : July 9, 2015
Last Update Posted : September 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This partially randomized phase I/II trial studies the side effects and best dose of anakinra when given together with lenalidomide and dexamethasone in treating patients with early stage multiple myeloma. Biological therapies, such as lenalidomide and anakinra, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide and dexamethasone are more effective with or without anakinra in treating patients with multiple myeloma.

Condition or disease Intervention/treatment Phase
Indolent Plasma Cell Myeloma Plasma Cell Myeloma Smoldering Plasma Cell Myeloma Biological: Anakinra Drug: Dexamethasone Other: Laboratory Biomarker Analysis Drug: Lenalidomide Other: Placebo Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 2016
Actual Primary Completion Date : June 5, 2019
Actual Study Completion Date : September 13, 2019


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
Biological: Anakinra
Given SC
Other Names:
  • Kinaret
  • Kineret
  • rIL-1ra
  • rIL1RN

Drug: Dexamethasone
Given PO
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

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.
Drug: Dexamethasone
Given PO
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Other: Placebo
Given SC
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy




Primary Outcome Measures :
  1. Incidence of adverse events, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ]
    The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

  2. Incidence of toxicity graded according to Common Toxicity Criteria [ Time Frame: Up to 5 years ]
    Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  3. MTD of lenalidomide, dexamethasone, and anakinra defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: 28 days ]
    Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  4. Response profile (Phase I) [ Time Frame: Up to 5 years ]
    A response is defined to be a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) noted as the objective status. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.

  5. Time to disease progression (TTP) (Phase II) [ Time Frame: Time from registration until the earliest date of documentation of disease progression, assessed at 2 years ]
    The primary analysis of TTP will be a comparison of arm A to arm B using a one-sided log-rank test between the two Kaplan-Meier curves.


Secondary Outcome Measures :
  1. Overall response rate (ORR) (Phase II) [ Time Frame: Up to 5 years ]
    ORR will be estimated by the number of patients with an objective status of sCR, CR, VGPR, or PR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated within each arm and compared between the arms using Fisher's exact test.

  2. Survival time (Phase II) [ Time Frame: Time from registration to death due to any cause, assessed up to 5 years ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier within each arm and compared between the arms using a one-sided log-rank test.



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:

  • 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

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): NCT02492750


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: John Lust Mayo Clinic

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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02492750     History of Changes
Other Study ID Numbers: MC138B
NCI-2015-01041 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RV-CL-MM-PI-004334
MC138B ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: July 9, 2015    Key Record Dates
Last Update Posted: September 16, 2019
Last Verified: June 2019
Additional relevant MeSH terms:
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Dexamethasone
Dexamethasone acetate
Lenalidomide
BB 1101
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
Interleukin 1 Receptor Antagonist Protein
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones