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Treatment for Elderly Fit Newly Diagnosed Multiple Myeloma Patients Aged Between 65 and 80 Years

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ClinicalTrials.gov Identifier: NCT03742297
Recruitment Status : Recruiting
First Posted : November 15, 2018
Last Update Posted : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation

Brief Summary:

The study is designed as a randomized, controlled, open-label, assessor blind, multicenter superiority trial with three parallel groups, and primary endpoint of immunophenotypic complete responses at 18 months after randomization. Block randomization will be performed with a 1:1:1 allocation ratio.

Patients will be randomized up front to 3 arms. Patients will receive "standard" PETHEMA arm for fit elderly VMP x 9 + Rd x 9 (arm 1, control arm), a KRd regimen (arm 2a) (18 cycles) or a Carfilzomib-lenalidomida-dexametasona regimen combined with DARATUMUMAB (arm 2b) (18 cycles).


Condition or disease Intervention/treatment Phase
Newly Diagnosed Multiple Myeloma Drug: Lenalidomide. Drug: Carfilzomib Drug: Bortezomib Drug: Daratumumab Drug: Dexamethasone Drug: Prednisone Drug: Melphalan Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Induction Therapy With Bortezomib-melphalan and Prednisone (VMP) Followed by Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab, 18 Cycles, Followed by Consolidation and Maintenance Therapy With Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple Myeloma Patients Aged Between 65 and 80 Years
Actual Study Start Date : October 22, 2018
Estimated Primary Completion Date : October 22, 2020
Estimated Study Completion Date : October 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Active Comparator: VMP x 9 + Lenalidomida-dexamethasone x 9
Bortezomib-melfalán-prednisone. Melfalán: 9mg/m2D1-4. Prednisone: 60mg/m2D1-4. Bortezomib: 1.3mg/m2 One 6 week cycleD1, 4, 8, 11, 22, 25, 29 and 32; followed by eight4-week cycleD1, 8, 15 and 22 Lenalidomida-dexametasona at low dose
Drug: Lenalidomide.
Lenalidomide

Drug: Bortezomib
Bortezomib

Drug: Dexamethasone
Dexamethasone

Drug: Prednisone
Prednisone

Drug: Melphalan
Melphalan

Experimental: Carfilzomib-lenalidomida-dexamethasone regimen
carfilzomib: 1 st cycle: 20mg/m2 day 1 and 36 mg/m2 days 2, 8, 9 & 15, 16. 2nd cycle: 36 mg/m2 days 1, 2, 8, 9 & 15, 16. Cycles 3-18: 56 mg/m2 days 1, 8 & 15.Lenalidomida: 25 mg, d1-21 Dexamethasone : 40 mg, d1, 8, 15, 2218 28-day cycle
Drug: Lenalidomide.
Lenalidomide

Drug: Carfilzomib
Carfilzomib

Drug: Dexamethasone
Dexamethasone

Experimental: Carfilzomib-lenalidomida-dexamethason with daratumumab
Carfilzomib: 1 st cycle: 20mg/m2 day 1 and 36 mg/m2 days 2, 8, 9 & 15, 16. 2nd cycle: 36 mg/m2 days 1, 2, 8, 9 & 15, 16. Cycles 3-18: 56 mg/m2 days 1, 8 & 15. Lenalidomida: 25 mg, d1-21 Dexamethasone: 40 mg, d1, 8, 15, 22 Daratumumab 16 mg/Kg IV Days 1, 8, 15, 22 of cycles 1-2; Days 1 and 15 of cycles 3 and 4; Day 1 of cycles 5 to 18
Drug: Lenalidomide.
Lenalidomide

Drug: Carfilzomib
Carfilzomib

Drug: Daratumumab
Daratumumab

Drug: Dexamethasone
Dexamethasone




Primary Outcome Measures :
  1. Efficacy in terms of numbers of compleat responses [ Time Frame: 18 months ]
    Rate of immunophenotypic complete responses at 18 months, of the standard treatment in Spain for newly diagnosed multiple myeloma patients not candidates to stem cell transplantation,



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Ages Eligible for Study:   65 Years to 80 Years   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed multiple myeloma patients who require start active treatment according to the IMWG published in 2014
  • Age between 65 and 80 years, both included
  • Fit patient assessed using the comprehensive health status assessment scale (Geriatric Assessment in Hematology, GAH scale, annex 11) (0-94 points GAH scale). Patients with a punctuation ≤42 will be included.
  • Signed informed consent
  • Patients must have measurable disease, defined as follows:

For secretory Multiple Myeloma, measurable disease is defined as the presence of quantifiable monoclonal component, ≥ 0.5 g/dL or, the urine light chains excretion is 200 mg/24h or higher.

For poor secretory or non secretory Multiple Myeloma, the level of the affected serum free light chain must be ≥ 10 mg/dL (≥ 100 mg/L, with an abnormal free light-chain ratio)

  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
  • Life expectancy more than 3 months
  • Adequate organ functions:

Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed only if they are due to BM infiltration.

Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x Upper Limit of Normal.

Total bilirubin: ≤2 x Upper Limit of Normal. Serum creatinine ≤ 2 mg/dl. Calcium ≤14mg/dl or corrected serum calcium ≤14mg/dl in patients whose albumin level is out of range Left ventricle ejection fraction ≥ 40%

  • At the discretion of the investigator patient must be able to adhere to all study requirements.
  • Male patients that receives lenalidomide should commit to use of a condom while taking the study drug every time he has sexual contact with a pregnant female of female of childbearing potential even if he has undergone a successful vasectomy; or practice complete abstinence (when this is the preferred and usual lifestyle of the subject); including during periods of dose interruptions and for at least 30 days after treatment completion. Also males under lenalidomide should commit not to donate semen or sperm during study drug treatment, including during periods of dose interruptions, and for at least 90 days after treatment completion.

NOTE: Given the age of patients to be included on this Clinical Trial (between 65 and 80 years, both included), there is no possibility of Females of Childbearing Potential (FCBP), therefore the Pregnancy Prevention Program (annex 12) has been modified accordingly.

Exclusion Criteria:

  • Patients older than 81 years or younger than 65
  • Patients that do not qualify for fit according to the GAH scale (annex 11) (>43 points GAH scale)
  • Patients who have previously received treatment for multiple myeloma, except for steroid pulses in case of emergency, the administration of bisphosphonates or antialgesic radiotherapy or due to the presence of plasmacytomas requiring some emergency.
  • Men who does not agree to use a condom every time he has sexual contact with a pregnant female or female of childbearing potential, even if he has undergone a successful vasectomy, or men who does not agree to practice complete abstinence (if this is the preferred and usual lifestyle of the subject).
  • Left ventricular ejection fraction <40% Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for ≥ 5 years.
  • Other relevant diseases or adverse clinical conditions:

Myocardial infarction within the 6 months prior to inclusion in the clinical trial A NYHA functional class III-IV, heart failure, uncontrolled angina, uncontrolled ventricular arrhythmia or acute ischemia detected electrocardiographically or conduction system anomalies.

History of significant neurological or psychiatric disorders. Active infection. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).

Poorly controlled arterial hypertension. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.

  • Human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or active hepatitis C infection
  • Limitation of the patient's ability to comply with the treatment or follow-up protocol.
  • Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
  • Patients having a peripheral neuropathy ≥ Grade 2 within the 14 days prior to inclusion.
  • Known hypersensibility to any of the study drugs or their excipients.
  • Patients treated with any investigational drug during the previous 30 days.
  • Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
  • Patients who are unable or unwilling to undergo antithrombotic therapy.
  • Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEVI) less than 50%.

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): NCT03742297


Contacts
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Contact: M Victoria Mateos, Dr +34923 29 11 00 mvmateos@usal.es

  Show 64 Study Locations
Sponsors and Collaborators
PETHEMA Foundation
Investigators
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Study Chair: Jesús F San Miguel Clínica Universidad de Navarra
Study Chair: Joan Blade, Dr Hospital Clinic of Barcelona
Study Chair: Juan Jose Lahuerta, Dr Hospital 12 de Octubre

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Responsible Party: PETHEMA Foundation
ClinicalTrials.gov Identifier: NCT03742297     History of Changes
Other Study ID Numbers: GEM2017FIT
First Posted: November 15, 2018    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
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
Dexamethasone
Dexamethasone acetate
Prednisone
Lenalidomide
Bortezomib
Melphalan
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids