Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

IPD in RRMM Characterized With Genomic Abnormalities of Adverse Prognostic (IFM2014-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03683277
Recruitment Status : Not yet recruiting
First Posted : September 25, 2018
Last Update Posted : September 25, 2018
Sponsor:
Collaborators:
AXONAL
Nantes University Hospital
University Hospital, Grenoble
EURAXI
Information provided by (Responsible Party):
Intergroupe Francophone du Myelome

Tracking Information
First Submitted Date  ICMJE August 23, 2018
First Posted Date  ICMJE September 25, 2018
Last Update Posted Date September 25, 2018
Estimated Study Start Date  ICMJE October 1, 2018
Estimated Primary Completion Date October 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2018)
Time to disease progression (TTP) to IPD in RRMM with adverse Genomic Abnormalities [ Time Frame: from Cycle 1 Day 1 of Induction phase (each Cycle is 21 days) until documented disease progression or death due to disease progression, whichever came first, assessed through study completion, an average of 18 months ]
Time to progression (TTP), defined as time from the first induction cycle to confirmed progressive disease (PD) per the International Myeloma Working Group criteria, or death due to progressive disease, whichever occurs first. It is noted that the events (PD or death due to PD) may include those that occur in the maintenance phase. The analysis will be performed on an Intent-To-Treat (ITT) basis and then per protocol
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2018)
  • Incidence of Serious Adverse Events and Averse Events (grade 3 and higher) as assessed by CTCAE version 4.0, dose reduction and discontinuation [ Time Frame: after the 10th patient has completed the first cycle of treatment (Cycle is 21 days), an average of 5 months after the beginning of the study and then every 6 months through study end ]
    A safety Analysis will be performed after the 10th patient enrolled has finished the first cycle of treatment, without any enrollment break. The Independent Data Monitoring Committee (DMC) will then analyzed the following:
    • Frequency of Total Serious Adverse Events (SAE)
    • Frequency of Adverse Events (AEs) Grade 3 or higher
    • Frequency of dose reductions
    • Frequency of dose discontinuations
    Data Monitoring Committee. No enrollment break is planned unless requested by the DMC. The DMC will analyze: The interim safety analysis after the10th patient enrolled has finished the first cycle of treatment. Safety review along study if asked by the sponsor.
  • plasma concentrations of ixazomib after twice-weekly dosing in combination with Pomalidomide and Dexamethasone [ Time Frame: from Cycle 1 Day 1 to Cycle 5 day 1 of Induction phase (each cycle is 21 days) ]
    Sparse Pharmacokinetics samples for the measurement of plasma concentrations of ixazomib will be collected in this study for the purposes of population PK and exposure-response analyses
  • Overall Response rate (ORR, Partial Response and better) to IPD [ Time Frame: after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study ]
    Post-induction and post-maintenance overall response rate (ORR) defined as the proportions of subjects who have achieved PR or better by the end of treatment per the IMWG criteria
  • Very Good Partial Response (VGPR) rate to IPD [ Time Frame: after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study ]
    rate of VGPR or better, defined as the proportions of subjects who have achieved PR or better by the end of induction phase per the IMWG criteria
  • Complete Response (CR) rate to IPD [ Time Frame: after completion of induction treatment of the last patient included, an average of 2 years after the beginning of the study and post maintenance treatment of the last patient included, an average of 3 years and half after the beginning of the study ]
    CR rate defined as the proportions of subjects who have achieved CR by the end of Induction phase per IMWG criteria
  • Time to response and Response duration to IPD for responders [ Time Frame: at the end of the study treatment, an average of 3 years and half after the beginning of the study ]
    at the end of the study, time to response and level of response to IPD for responders patients will be analyzed
  • Clinical benefit response rate to IPD [ Time Frame: at the end of the study treatment, an average of 3 years and half after the beginning of the study ]
    Clinical Benefit rate (CBR), Minor Response (MR) and better will be analysed at the end of the study
  • Overall Survival (OS) to IPD [ Time Frame: from the start of study treatment to death or the termination of the study, whichever came first, an average of 5 years ]
    Overall Survival (OS) rate defined as the time in months from start of treatment and death or the termination of the study, whichever came first
  • Progression free survival (PFS) to IPD [ Time Frame: from the start of study treatment to disease progression, an average of 3 years and half ]
    Progression free survival (PFS) defined as the time in months from start of treatment and disease progression
  • Event Free survival (EFS) to IPD [ Time Frame: from the start of study treatment to death or the termination of the study, whichever came first, an average of 5 years ]
    Event Free survival (EFS) to IPD defined as the time in months from start of treatment and disease recurrence or onset of disease symptoms
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 22, 2018)
  • Response rate to IPD with to genomic abnormalities in the bone marrow tumor plasma cells. [ Time Frame: from the start of study treatment to the termination of the study, an average of 5 years ]
    Response rate defined as the proportions of subjects who show a PR or better from start of treatment and the termination of the study
  • Survival rate to IPD with to genomic abnormalities in the bone marrow tumor plasma cells. [ Time Frame: from the start of study treatment to the termination of the study, an average of 5 years ]
    Survival rate defined as the proportions of subjects who are still alive at the termination of the study
  • Define the molecular characteristics of the 2 groups, ER and PR to IPD [ Time Frame: from the start of study treatment to the termination of the study, an average of 5 years ]
    Definition of molecular characteristics assessed by performing whole exome sequencing (WES) and RNA-sequencing (RNA-seq)
  • Compare the molecular characteristics of the 2 groups, ER and PR to IPD [ Time Frame: from the start of study treatment to the termination of the study, an average of 5 years ]
    Comparison of molecular characteristics by performing whole exome sequencing (WES) and RNA-sequencing (RNA-seq)
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE IPD in RRMM Characterized With Genomic Abnormalities of Adverse Prognostic
Official Title  ICMJE Multicenter Open Label Phase 2 Single Arm Study of Ixazomib, Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma Characterized With Genomic Abnormalities of Adverse Adverse Prognostic
Brief Summary This study is a Multicenter, Open-label, Phase II study of ixazomib, plus Pomalidomide and Dexamethasone regimen (IPD) in RRMM with adverse Genomic Abnormalities.
Detailed Description

There is no escalation dose study, the maximum tolerated dose has already been determined in previous phase 1 escalation dose studies. The proposed dose of dexamethasone is considered standard. Patients will receive the IPd regimen until progression.

The hypothesis is that this IPd regimen based combination will eventually improve time to disease progression, with no additional toxicity, as compared to other available regimens, in this subgroup of patients with myeloma characterized with a very adverse prognosis.

Study design. This trial will study the efficacy and safety of IPd regimen in Relapsed and Refractory Multiple Myeloma with adverse Genomic Abnormalities until progression in 2 separate phases.

  • Induction phase: 17 cycles - 21-days cycles Ixazomib 3 mg D1, D4, D8 and D11 Pomalidomide 4mg D1 to D14 Dexamethasone 40 mg/d D1, D8 and D15 if patient aged <75 years Dexamethasone 20 mg/d D1, D8 and D15 if patient aged ≥ 75 years
  • Maintenance phase: until progression - 28-days cycles Ixazomib 4mg D1, D8 and D15 Pomalidomide 4mg D1 to D21
  • It is not planned for the patients to receive autologous stem-cell transplantation as part of the study trial
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
All the patients will receive the same treatment until progression desease
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Multiple Myeloma
  • Relapsed and Refractory Multiple Myeloma
  • Genetic Condition
Intervention  ICMJE Drug: Ixazomib/Pomalidomide/Dexamethasone

Treatment with association of Ixazomib, Pomalidomide and Dexamethasone (IPD)

Induction phase : 21-days cycles - maximum of 17 cycles Ixazomib (tablets) 3 mg D1, D4, D8 and D11 Pomalidomide (tablets) 4mg D1 to D14 Dexamethasone (tablets) 40 mg/d D1, D8 and D15 if patient aged <75 years Dexamethasone (tablets) 20 mg/d D1, D8 and D15 if patient aged ≥ 75 years

Treatment with association of Ixazomib and Pomalidomide (IP) Maintenance phase : 28-days cycles until disease progression Ixazomib (tablets) 4mg D1, D8 and D15 Pomalidomide (tablets) 4mg D1 to D21

Other Name: Multicentric, phase 2, RRMM, refractory, relapse, myeloma
Study Arms  ICMJE Experimental: Ixazomib/Pomalidomide/Dexamethasone

Single arm treatment organized in 2 separate phases

Induction phase : association of Ixazomib, Pomalidomide & Dexamethasone (IPD) 21-days cycles - maximum of 17 cycles Ixazomib (tablets) 3 mg D1, D4, D8 and D11 Pomalidomide (tablets) 4mg D1 to D14 Dexamethasone (tablets) 40 mg/d D1, D8 and D15 if patient aged <75 years Dexamethasone (tablets) 20 mg/d D1, D8 and D15 if patient aged ≥ 75 years

Maintenance phase : association of Ixazomib and Pomalidomide (IP) 28-days cycles until disease progression Ixazomib (tablets) 4mg D1, D8 and D15 Pomalidomide (tablets) 4mg D1 to D21

Intervention: Drug: Ixazomib/Pomalidomide/Dexamethasone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 22, 2018)
70
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2023
Estimated Primary Completion Date October 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female patients 18 years or older.
  2. Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  3. Life expectancy > 3 months.
  4. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2.
  5. Presence - at diagnosis or at relapse - of one of the following adverse genomic abnormalities determined using Interphase fluorescence in situ hybridization and Single nucleotide polymorphism (FISH/SNP) techniques at a significant rate validated centrally by Pr AVET - LOISEAU:

    • deletion 17p
    • and/ or translocation (4; 14)
  6. Must have an RRMM and have received a Lenalidomide line of treatment
  7. Must have a Progressive Multiple Myeloma (MM) according to IMWG consensus recommendations for multiple myeloma treatment response criteria (DURIE 2007, RAJKUMAR 2011) :

    • Increase of 25% from lowest response value in any one of the following:
    • Serum M-component (absolute increase must be ≥ 0.5 g/dL),
    • Urine M-component (absolute increase must be ≥ 200 mg/24 hours),
    • Only in subjects without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC (Free Light-Chain) levels (absolute increase must be >10 mg/dL)
    • Bone marrow plasma cell percentage: the absolute percentage must be >10%
    • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
    • Development of hypercalcemia (corrected serum calcium >11.5 mg/dL) that can be attributed solely to the PC (Plasma Cell) proliferative disorder
  8. Must have a measurable disease as defined by the following:

    • IgG (immunoglobulin G) and IgA (immunoglobulin A) (serum M-component > 5g/l)
    • IgD (immunoglobulin D) (serum M-component > 0.5g/l)
    • Light chain (Bence Jones > 200mg/24h)
    • For MM without measurable serum or urine M protein, involved FLC ≥100 mg/l and FLC abnormal ratio.
  9. Patients must meet the following clinical laboratory criteria:

    • Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
    • Total bilirubin ≤1.5 x the upper limit of the normal range (ULN).
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
    • Calculated creatinine clearance ≥ 30 mL/min MDRD (Modification of Diet in Renal Disease) formula should be used for calculating creatinine clearance values: http://mdrd.com/
  10. Able to undergo antithrombotic prophylactic treatment. HBPM (low weight heparin) is preferred. In case of anti-Vitamin K Agent, INR (international normalized ratio) must be used
  11. Female patients who:

    • Have been postmenopausal for at least 2 years before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

    Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  12. Patients agree:

    • not to share study medication with any other person and to return all unused study drugs to the investigator.
    • to abstain from donating blood while taking the study drug therapy and for one week following discontinuation of the study drug therapy.
  13. Must be able to adhere to the study visit schedule and other protocol requirements including the pregnancy prevention program as detailed in section 13.4 of protocol
  14. Affiliated with an appropriate social security system.

Exclusion Criteria:

  1. Any other uncontrolled medical condition or comorbidity that might interfere with subject's participation.
  2. Patients not having receive Lenalidomide
  3. Pregnant or breast feeding females
  4. Known positive for HIV or active hepatitis type B or C.
  5. Patients with non-secretory MM
  6. Patient with terminal renal failure that require dialysis and clearance creatinine < 30ml/min
  7. Prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for ≥ 5 years.
  8. Prior local irradiation within two weeks before first dose*

    *However, an exception (that is patients allowed to remain in the treatment phase of the study) is made for radiation therapy to a pathological fracture site to enhance bone healing or to treat post-fracture pain that is refractory to narcotic analgesics because pathologic bone fractures do not by themselves fulfill a criterion for disease progression.)

  9. Evidence of central nervous system (CNS) involvement
  10. Unable to take corticotherapy at study entry, Ixazomib or pomalidomide
  11. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
  12. Ongoing Cardiac dysfunction: specify e.g. uncontrolled hypertension, MI (Myocardial Infarction) within 6 months, unstable Angina pectoris, Cardiac arrhythmia Grade 2 or higher
  13. Patients planned to receive a transplantation while on IPd protocol
  14. Patients who have had Ixazomib and Pomalidomide therapy as a previous line
  15. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
  16. Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
  17. Inability or unwillingness to comply with birth control requirements
  18. Unable to take antithrombotic medicines at study entry
  19. Major surgery within 14 days before enrollment.
  20. Systemic treatment, within 14 days before the first dose of ixazomib and Pomalidomide, with strong CYP3A (Cytochrome P450 3A) inducers (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort.
  21. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  22. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  23. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib and Pomalidomide including difficulty swallowing.
  24. Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
  25. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
  26. Subjects under juridical protection guardianship or tutelage measure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Chantal NOBILI ESCRIVA +33 (0)7874755154 c.nobili@myelome.fr
Contact: Sarah HORN +33 (0)6 27 31 69 10 shorn@axonal.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03683277
Other Study ID Numbers  ICMJE IFM 2014-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Intergroupe Francophone du Myelome
Study Sponsor  ICMJE Intergroupe Francophone du Myelome
Collaborators  ICMJE
  • AXONAL
  • Nantes University Hospital
  • University Hospital, Grenoble
  • EURAXI
Investigators  ICMJE
Principal Investigator: Xavier LELEU Poitiers University Hospital
PRS Account Intergroupe Francophone du Myelome
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP