ClinTrial Refer

Registration Number
NCT03606577

Scientific Title
An Intensive Program With Quadruplet Induction and Consolidation Plus Tandem Autologous Stem Cell Transplantation in Newly Diagnosed High Risk Multiple Myeloma Patients: a Phase II Study of the Intergroupe Francophone du Myélome "IFM 2018-04"

According to international guidelines, upfront therapy for transplant eligible myeloma
      patients should include triplet induction containing proteasome inhibitor and
      immunomodulatory agent, autologous stem cell transplant, PI+Imid based triplet consolidation
      and lenalidomide maintenance. Despite this approach, virtually all MM patients experience
      disease relapse, especially those with High Risk disease defined by adverse cytogenetic
      abnormalities (i.e. del(17p), or t(14;16) or t(4;14)) detected by FISH and/or SNP arrays.
      Indeed, HR myeloma is associated with poorer progression free survival and overall survival
      and frontline therapy should therefore be improved for this subset of HR patients. The
      primary objective of this prospective multicenter, open label, interventional phase 2 trial
      is to evaluate the feasibility of an intensive program including quadruplet induction and
      consolidation, tandem autologous stem cell transplantation and maintenance in newly diagnosed
      multiple myeloma patients presenting with HR cytogenetic. Quadruplet induction and
      consolidation include carfilzomib, lenalidomide, dexamethasone and daratumumab. Maintenance
      will include lenalidomide and daratumumab. Secondary objectives will include efficacy
      parameters (i.e. response rate, minimal residual disease, safety, progression free survival,
      overall survival).

1. Male or female subjects, 18 years of age or older, younger than 66 years (< 66 years)
    2. Voluntary written informed consent must be given before performance of any       study-related procedure not part of normal medical care, with the understanding that       the subject may withdraw consent at any time without prejudice to future medical care.
    3. Subject must have documented multiple myeloma satisfying the Diagnostic criteria for       symptomatic Myelome Multiple and measurable disease as defined by:   -  Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven            plasmacytoma AND any one or more of the following myeloma defining events:        -  Hypercalcemia: serum calcium > 0.25 mmol/L higher than ULN or > 2.75 mmol/L        -  Renal insufficiency: creatinine clearance < 40mL/min or serum creatinine >                 177 μmol/L        -  Anemia: hemoglobin > 2 g/dL below the lower limit of normal or hemoglobin <                 10 g/dL        -  Bone lesions: one or more osteolytic lesions on skeletal radiography, CT or                 PET-CT        -  Clonal bone marrow plasma cell percentage ≥ 60%        -  Involved: uninvolved serum free light chain ratio ≥ 100        -  Superior 1 focal lesion on MRI studies   -  Measurable disease as defined by the following: M-component ≥ 5g/l, and/or urine M-component ≥ 200 mg/24h and/or serum Free Light       Chain ≥ 100 mg/l.
    4. Newly diagnosed subjects eligible for high dose therapy and autologous stem cell       transplantation
    5. Subject must have high risk disease according to FISH analysis: del(17p), or t(14;16)       or t(4;14). The FISH-positivity cut-off value for defining the presence of del(17p) in       this study is 50%
    6. Karnofsky performance status score ≥ 50%
    7. Women of childbearing potential must have a negative serum or urine pregnancy test       within 10 to 14 days prior to therapy and repeated within 24 hours before starting       study drug. They must commit to continued abstinence from heterosexual intercourse or       begin 2 acceptable methods of birth control used at the same time, beginning at least       4 weeks before initiation of lenalidomide treatment and continuing for at least 30       days after the last dose of Lenalidomide. Women must also agree to notify pregnancy or       doubt upon pregnancy during the study.
    8. Men must agree to not father a child and agree to use a latex condom during therapy       and for 4 weeks after the last dose of study drug, even if they have had a successful       vasectomy, if their partner is of childbearing potential.
    9. Subject must have pretreatment clinical laboratory values meeting the following       criteria during the Screening Phase (Lab tests should be repeated if done more than 15       days before C1D1):   1. Hemoglobin ≥ 7.5 g/dL. Prior red blood cell transfusion or recombinant human            erythropoietin use is permitted;   2. Absolute neutrophil count ≥ 1.0 Giga/l (GCSF use is permitted);   3. ASAT ≤ 3 x ULN;   4. ALAT ≤ 3 x ULN;   5. Total bilirubin ≤ 3 x ULN (except in subjects with congenital bilirubinemia, such            as Gilbert syndrome, direct bilirubin ≤ 1.5 x ULN);   6. Calculated creatinine clearance ≥ 40 mL/min/1.73 m² ;   7. Corrected serum calcium ≤ 14 mg/dL; or free ionized calcium ≤6.5 mg/dL;   8. Platelet count ≥ 50 Giga/l for subjects in whom < 50% of bone marrow nucleated            cells are plasma cells; otherwise platelet count > 50 Giga/l (transfusions are            not permitted to achieve this minimum platelet count).
   10. Affiliation with French social security system or beneficiary from such system

1. Subjects must not have been treated previously with any systemic therapy for multiple       myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify       the subject (the maximum dose of corticosteroids should not exceed the equivalent of       160 mg of dexamethasone in a 2-week period). Two weeks must have elapsed since the       date of the last radiotherapy treatment. Enrolment of subjects who require concurrent       radiotherapy (which must be localized in its field size) should be deferred until the       radiotherapy is completed and 2 weeks have elapsed since the last date of therapy
    2. Subject has received daratumumab or other anti-CD38 therapies previously
    3. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined       significance, smoldering multiple myeloma, or solitary plasmacytoma.
    4. Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in       which IgM M-protein is present in the absence of a clonal plasma cell infiltration       with lytic bone lesions.
    5. Subject has had plasmapheresis within 28 days of C1D1.
    6. Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
    7. Myocardial infarction within 6 months prior to enrolment according to NYHA Class III       or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias,       or electrocardiographic evidence of acute ischemia or active conduction system       abnormalities
    8. Uncontrolled hypertension
    9. Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced       Expiratory Volume (FEV1) in 1 second < 50% of predicted normal. Note that FEV1 testing       is required for patients suspected of having COPD and subjects must be excluded if       FEV1 < 50% of predicted normal.
   10. Subjects with a history of moderate or severe persistent asthma within the past 2       years, or with uncontrolled asthma of any classification at the time of screening       (Note that subjects who currently have controlled intermittent asthma or controlled       mild persistent asthma are allowed in the study).
   11. Subject has plasma cell leukemia (according to WHO criterion: ≥ 20% of cells in the       peripheral blood with an absolute plasma cell count of more than 2 × 10^9/L) or       polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes       syndrome.
   12. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong       inhibitors of CYP3A (as clarithromycin, telithromycin, itraconazole, voriconazole,       ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (as rifampin,       rifapentine, rifabutin, carbamazepine, phenytoin, fosphenytoin phenobarbital), or use       of Ginkgo biloba or St. John's wort within 14 days before the first dose of study       treatment.
   13. Known intolerance to steroid therapy
   14. History of hypersensitivity to any of the study medications, their analogues, or       excipients in the various formulations, or to study-required co medication
   15. Subject has had major surgery within 2 weeks before the first dose of study treatment       or will not have fully recovered from surgery, or has surgery planned during the time       the subject is expected to participate in the study. Kyphoplasty or Vertebroplasty are       not considered major surgery.
   16. Clinically relevant active infection or serious co-morbid medical conditions
   17. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in       situ cervical, breast or prostate cancer free of disease since 5 years.
   18. Female subject who is pregnant or breast-feeding + male and female refusing birth       control conditions
   19. Serious medical or psychiatric illness likely to interfere with participation in study
   20. Uncontrolled diabetes mellitus
   21. Known HIV infection; Known active hepatitis B or C viral infection; or other ongoing       uncontrolled infection
   22. Incidence of gastrointestinal disease that may significantly after the absorption of       oral drugs
   23. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
   24. Person under guardianship, trusteeship or deprived of freedom by a judicial or       administrative decision

Trial Location Name

Address

Status

CHD Vendée la Roche sur Yon

Centre Hospitalier Départemental Vendée, Boulevard Stéphane Moreau, 85000 La Roche-sur-Yon, France

Closed

Primary Contact : Nadine Morineau (LYSA), nadine.morineau@chd-vendee.fr , N/A

Secondary Contact : Mourad Tiab (IFM), mourad.tiab@chd-vendee.fr , +33 251446173

CHRU de Tours / Centre Henri Kaplan

2 Boulevard Tonnellé, Tours, France

Closed

Primary Contact : Caroline Dartigeas (LYSA), c.dartigeas@chu-tours.fr , +33 2 47 47 47 47

Secondary Contact : Lotfi Benboubker (IFM), l.benboubker@chu-tours.fr , +33 247473712

CHRU Nantes - Hôtel Dieu

1 Place Alexis-Ricordeau, Nantes, France

Closed

Primary Contact : Steven Le Gouill (LYSA), steven.legouill@chu-nantes.fr , n/a

Secondary Contact : Philippe Moreau (IFM), philippe.moreau@chu-nantes.fr , +33 240083269

CHU Bordeaux- Hopital Haut Leveque - Centre Francois Magendie

Av. Magellan, Pessac, France

Closed

Primary Contact : Krimo Bouabdallah (LYSA), krimo.bouabdallah@chu-bordeaux.fr , +33 5 56 79 56 79

Secondary Contact : Cyrille Hulin (IFM) , cyrille.hulin@chu-bordeaux.fr , +33 557656511

CHU Caen Cote de Nacre

Avenue de la Côte de Nacre, Caen, France

Closed

Primary Contact : Gandhi Damaj (LYSA), damaj-gl@chu-caen.fr , 231272140

Secondary Contact : Magaret Macro (IFM), macro-m@chu-caen.fr , +33 231272122

CHU Dijon le Bocage

Rue Paul Gaffarel, Dijon, France

Closed

Primary Contact : Olivier Casasnovas (LYSA), olivier.casasnovas@chu-dijon.fr , n/a

Secondary Contact : Denis Caillot (IFM), denis.caillot@chu-dijon.fr , +33 380295041

CHU Grenoble Albert Michallon

Avenue Maquis du Grésivaudan, La Tronche, France

Closed

Primary Contact : Remy Gressin (LYSA), rgressin@chu-grenoble.fr , +33 4 76 76 75 75

Secondary Contact : Clara Mariette (IFM) , cmariette@chu-grenoble.fr , +33 476765755

CHU Lille - Hopital Claude Huriez

Rue Michel Polonowski, 59000 Lille, France

Closed

Primary Contact : Franck Morschhauser (LYSA), franck.morschhauser@chru-lille.fr , +33 3 20 44 59 62

Secondary Contact : Thierry Facon (IFM) , thierry.facon@chru-lille.fr , +33 320445713

CHU Lyon Sud

Chemin du Grand Revoyet, Pierre-Bénite, France

Closed

Primary Contact : Gilles Salles (LYSA), gilles.salles@chu-lyon.fr , 04.78.86.43.35

Secondary Contact : Lionel Karlin (IFM), lionel.karlin@chu-lyon.fr

CHU Rennes Pontchaillou

2 Rue Henri le Guilloux, Rennes, France

Closed

Primary Contact : Thierry Lamy de la Chappelle, thierry.lamy-de-la-chapelle@univ-rennes1.fr , +33 2 99 28 43 21

Secondary Contact : Olivier Decaux (IFM), olivier.decaux@chu-rennes.fr , +33 299283676

Hôpitaux de Brabois - CHRU de Nancy

Rue du Morvan, Vandœuvre-lès-Nancy, France

Closed

Primary Contact : Plerre Feugier (LYSA), p.feugier@chru-nancy.fr , +33 3 83 85 85 85

Secondary Contact : Lauriane Clement Filliatre (IFM), la.clement@chru-nancy.fr , +33 383155166

IUCT Oncopole Toulouse

1 Av. Irène Joliot-Curie, Toulouse, France

Closed

Primary Contact : Lucie Oberic (LYSA), oberic.lucie@iuct-oncopole.fr , +33 0531155050

Secondary Contact : Michel Attal (IFM), attal.michel@iuct-oncopol.fr , +33 0531155001

Nantes University Hospital

Back to List/Filter

to List/Filter