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Trial record 34 of 495 for:    LENALIDOMIDE AND every 28 days

Carfilzomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in High- Risk SMM (HO147SMM)

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ClinicalTrials.gov Identifier: NCT03673826
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : November 20, 2018
Sponsor:
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland

Brief Summary:
Randomized (2:1) multi-center open-label phase II trial. Patients with high-risk SMM will be enrolled on the study and treated with KRd combination (Cycles 1-9 carfilzomib 20/36 mg/m2, lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9) or Rd combination (Cycles 1-9 lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).

Condition or disease Intervention/treatment Phase
Smouldering Myeloma Drug: Carfilzomib Drug: Dexamethasone Drug: Lenalidomide Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Carfilzomib, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma: A Randomized Phase II Study.
Actual Study Start Date : November 19, 2018
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : October 2025


Arm Intervention/treatment
Experimental: Arm A
Rd combination (Cycles 1-9 lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).
Drug: Dexamethasone
4 cycles 20 mg days 1,2,8,9,15,16,22,23 followed by 5 cycles 10mg days 1,2,8,9,15,16,22,23

Drug: Lenalidomide
9 cycles 25mg days 1-21 followed by 24 extended dosing cycles 10mg days 1-21

Experimental: Arm B
KRd combination (Cycles 1-9 carfilzomib 20/36 mg/m2, lenalidomide 25 mg, dexamethasone 20 mg cycles 1-4 and 10 mg cycles 5-9); followed by extended lenalidomide dosing (10 mg days 1-21 of a 28 day cycle for 24 cycles).
Drug: Carfilzomib
9 cycles 20/36mg/m2 days 1,2,8,9,15,16

Drug: Dexamethasone
4 cycles 20 mg days 1,2,8,9,15,16,22,23 followed by 5 cycles 10mg days 1,2,8,9,15,16,22,23

Drug: Lenalidomide
9 cycles 25mg days 1-21 followed by 24 extended dosing cycles 10mg days 1-21




Primary Outcome Measures :
  1. Progression-free survival rate [ Time Frame: Until 5 years after randomization or death, whatever comes first ]
    Time from study entry to progression or death, whichever comes first


Secondary Outcome Measures :
  1. MRD status [ Time Frame: 9 months ]
    MRD assessment by immunophenotyping in bone marrow after induction cycles 4 and 9

  2. Progression-free survival-2 (PFS2), [ Time Frame: Until 5 years after randomization or death, whatever comes first ]
    Time from randomization to progression after second-line treatment or death, whichever comes first

  3. Duration of response (DOR), [ Time Frame: Until 5 years after randomization or death, whatever comes first ]
    Time from response to progression or death, whichever comes first

  4. Overall survival (OS) [ Time Frame: Until 5 years after randomization or death, whatever comes first ]
    Time from study entry to death from any cause. Patients still alive at the date last contact will be censored.

  5. MRD status correlation [ Time Frame: Until 5 years after randomization or death, whatever comes first ]
    Correlation of MRD status with PFS, PFS2, DOR and OS

  6. Toxicity of combination therapy with Carfilzomib. Lenalidomide and Dexamethasone [ Time Frame: Through induction treatment and extrended treatment, up to 3 years after randomization ]
    Measured by tabulation of the incidence of adverse events with CTCAE grade 1 or more, separately for induction treatment and for extended treatment, by randomization arm.



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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

  • Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria(20):
  • Serum M-protein ≥3.0 g/dl, or urinary monoclonal protein >500 mg per 24 hours, and/or monoclonal bone marrow plasma cells ≥10-60 %
  • Absence of CRAB symptoms:
  • anemia: Hemoglobin <6.2 mmol/L (10 g/dl) or a hemoglobin value of >1.2 mmol/L (2 g/dL) below the lower limit of normal
  • renal failure: serum creatinine > 2.0 mg/dL or creatinine clearance < 40 ml/min
  • hypercalcemia: serum calcium >0·25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2·75 mmol/L (>11 mg/dL)
  • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
  • Absence of myeloma defining events:
  • Involved/uninvolved serum free light chain ratio ≥100 with involved free light-chain concentration ≥10 mg/dl
  • Presence of 2 or more focal lesions by MRI (2 of which at least 5 mm)
  • Clonal bone marrow plasma cell percentage ≥60%
  • Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic2 or the PETHEMA1 criteria:
  • 3 factors of Mayo Clinic criteria:
  • Bone marrow plasma cells ≥10 %
  • Serum M-protein ≥ 3 g/dl
  • Serum free light-chain ratio <0.125 or >8
  • Or 2 factors of PETHEMA criteria:
  • Of the plasma cell population ≥95% abnormal plasma cells (decreased CD38 expression, expression of CD56, and absence of CD19 and/or CD45)
  • Immunoparesis, a reduction (below the lower normal limit) in the levels of 1 or 2 of the uninvolved immunoglobulins (Ig)
  • Measurable disease defined by any one of the following:
  • Serum monoclonal protein ≥ 1.0 g/dl
  • Urine monoclonal protein >200 mg/24 hour
  • Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
  • Age >18 years
  • WHO/ECOG performance status <2 (see Appendix C).
  • Patients must have normal organ and marrow function as defined below:
  • Absolute neutrophil count >1.0 x109 /L
  • Platelets ≥75 ×109 /L
  • Hemoglobin ≥10 g/dL (>6.2 mmol/l)
  • Total bilirubin <1.5 x institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) ≤3.0 × institutional upper limit of normal
  • Creatinine Clearance ≥ 50 ml/min. CrCl will be calculated by Cockcroft-Gault method. CrCl = [(140 - Age) x Mass (kg)] / [72 x Serum Creatinine (mg/dL)(x [0.85 if Female). If calculated CrCl based on Cockcroft-Gault method is <50 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be ≥50 ml/min.
  • Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide treatment; (see 9.1.4
  • Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all pre-menopausal women) (see 9.1.4.); Patients must be able to adhere to the requirements of the Lenalidomide Clinical Trial Pregnancy Prevention Plan;
  • Written informed consent
  • Patient is capable of giving informed consent

Exclusion criteria

  • Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)
  • Amyloid Light-chain (AL) amyloidosis
  • Patients who are receiving any other investigational agents.
  • Concurrent systemic treatment or prior therapy within 4 weeks for SMM (if a patient has received any previous SMM therapy this must be discussed with the Principal Investigator before inclusion in the trial).

Treatment with corticosteroids for other indications is permitted

  • Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
  • History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors.
  • Uncontrolled hypertension or diabetes
  • Pregnant or lactating females.
  • Significant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
  • Active hepatitis B or C infection
  • Known or suspected HIV infection
  • Incidence of gastrointestinal disease that would prevent absorption.
  • Significant neuropathy ≥Grade 3 or grade 2 with pain within 14 days of enrollment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection.
  • History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years
  • Major surgery within 1 month prior to enrollment
  • Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures as described at paragraph 9.1.4
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

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): NCT03673826


Contacts
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Contact: A. Broijl, Dr. +31 (0)10 7033123 a.broyl@erasmusmc.nl
Contact: O. Landgren, Dr. +1 646 449 1341 landgrec@mskcc.org

Locations
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Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands
Contact: A. Broyl         
Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Investigators
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Principal Investigator: A. Broijl Erasmus MC / HOVON

Additional Information:
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Responsible Party: Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier: NCT03673826     History of Changes
Other Study ID Numbers: HO147
2017-000555-10 ( EudraCT Number )
First Posted: September 17, 2018    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lenalidomide
Smoldering Multiple Myeloma
Neoplasms
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Hypergammaglobulinemia
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents