Protocoles de recherche clinique

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Les différentes études cliniques sur le myélome multiple ouvertes au recrutement l’Hôpital Maisonneuve-Rosemont sont présenté sur cette page. Ces études présentées excluent les études à venir et les études en cours, mais fermées au recrutement. L’affichage de ces différentes études cliniques se veut un outil pour favoriser la participation des patients aux études cliniques. Encore une fois, l’amélioration du pronostic des patients atteints d’un myélome multiple n’est pas le fruit du hasard, mais bien le résultat de la recherche, dont la participation des patients à la recherche clinique! 

Première ligne: éligible à la greffe
Première ligne: non éligible à la greffe
Myélome multiple récidivant et/ou réfractaire
Autres types d’études dont l’évaluation des traitements de support
SVP Communiquer directement avec nous afin de connaitre les études en cours de recrutement.
 

Référence de patients

Pour référer un patient à l’Hôpital Maisonneuve-Rosemont pour une étude clinique, veuillez communiquer avec Mme Nathalie Lachapelle, infirmière et coordonnatrice de recherche au 514-252-3400, poste 4471 ou par courriel au: nlachapelle.hmr@ssss.gouv.qc.ca

 

Pour des études sur le myélome multiple dans d’autres centres au Québec, veuillez vous référer au site du GEOQ.

Étude de phase 1/2 évaluant la tolérance et l’efficacité de l’isatuximab (anti-CD38) en combinaison avec le cemiplimab (ani-PD1) chez des patients atteints d’un myélome multiple en maladie récidivante

Critères d’inclusion:

  • Age ≥ 18 years
  • Patients must have a known diagnosis of multiple myeloma with evidence of measurable disease, as defined below:
    • Serum M-protein ≥1 g/dL (≥0.5 g/dL in case of IgA disease), AND/OR

    • Urine M-protein ≥200 mg/24 hours, OR

    • In the absence of measurable M-protein, serum immunoglobulin free light chain ≥10 mg/dL, and abnormal serum immunoglobulin kappa lambda free light chain ratio (<0.26 or >1.65)

  • Patients must have received prior treatment with an IMiD (for ≥2 cycles or ≥2 months of treatment) and a proteasome inhibitor (for ≥2 cycles or ≥2 months of treatment)
  • Patients must have received EITHER at least 3 prior lines of therapy (Note: Induction therapy and stem cell transplant ± maintenance will be considered as one line).

    OR

    Patients whose disease is double refractory to an IMiD and a PI (disease progression has occurred while on or within 60 days from last treatment)

  • Patient with refractory disease only, must have achieved MR or better with any anti-myeloma therapy (ie, primary refractory disease is not eligible)
  • Patients must have a disease that is refractory to the most recent prior line therapy (disease progression has occurred while on treatment or within 60 days from last treatment)

Critères d’exclusion:

  • Has any concurrent hematology malignancy other than multiple myeloma, including active primary AL amyloidosis and concomitant plasma cell leukemia.

  • Has prior exposure to isatuximab or participated clinical studies with isatuximab, or any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway.

  • Diagnosed or treated for another malignancy within 3 years prior to the study treatment with the exception of resected/ablated basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment, or low risk prostate cancer after curative therapy;

  • Evidence of other immune related disease /conditions, including: ongoing or recent (within 2 years) evidence of significant autoimmune disease that required systemic immunosuppressive treatment. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment; history of moderate immune-mediated acute drug reactions (eg, colitis, hepatitis, etc.).

  • History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation.

  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

  • Known to be HIV+, HBV+ or hepatitis A, B, or C active Infection.

  • Has allogenic HSC transplant.

  • Has prior exposure to treatment, including: any anti-myeloma drug treatment including dexamethasone within 14 days before study entry (90 days if prior anti-CD38 treatment); any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered major procedure), radiotherapy; any investigational drugs within 28 days or 5 half-lives from the 1st study treatment, whichever is longer.

  • Congestive heart failure (New York Heart Association class III to IV) myocardial infarction within 6 months or with reduced ejection fraction, symptomatic coronary artery disease, major clinically significant electrocardiogram (ECG) and echocardiogram abnormalities, significant ventricular arrhythmias.

  • Ongoing adverse events Grade ≥2 (excluding alopecia and those listed in eligibility criteria) from any prior anti-cancer therapy ≥(NCI-CTC v4.03).

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2.

  • Inadequate hematological function including:

    • Platelets <50,000/mm3. Patient should be platelet transfusion independent for 2 weeks prior to screening lab values),

    • ANC ≤1000/mm3 (1 x 109/L). (use of colony-stimulating factors to achieve these counts is allowed),

    • Hemoglobin <8.0 g/dL (patients may receive red blood cell transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidance).

  • Inadequate liver findings including:

    • Total bilirubin >2xULN,

    • AST and/or ALT >3xULN.

  • Inadequate renal function: estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 (MDRD Formula).

  • Corrected serum calcium >14 mg/dl (>3.5 mmol/l).

Étude de phase 3 comparant l’efficacité de la combinaison isatuximab (anti-CD38) avec le carfilzomib et dexamethasone versus carfilzomib et dexamethasone seuls chez des patients atteints d’un myélome multiple en maladie récidivante

Critères d’inclusion:

  • Patients will be considered for inclusion in this study if they meet all of the following criteria (all necessary baseline studies for determining eligibility must be obtained within 21 days prior to randomization):

    • Multiple myeloma.

    • Measurable disease: Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis.

    • Patient with relapsed and/or refractory MM with at least 1 prior line and no more than 3 prior lines.

Critères d’exclusion:

  • Less than 18 years.

  • Primary refractory MM defined as patients who have never achieved at least a MR with any treatment during the disease course.

  • Patient with free light chain (FLC) measurable disease only.

  • Patient with prior anti-CD38 mAb treatment with progression on or within 60 days after end of anti-CD38 mAb treatment or failure to achieve at least MR to treatment (ie, refractory to anti-CD38).

  • Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone.

  • Patient who has received any other investigational drugs or prohibited therapy for this study within 28 days prior to randomization.

  • Prior treatment with carfilzomib.

  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or H2 blockers, that would prohibit further treatment with these agents.

  • Patients with contraindication to dexamethasone.

  • Prior allogenic hematopoietic stem cell transplant with active graft versus host disease (any grade and/or being under immunosuppressive treatment within 2 months before randomization).

  • Known amyloidosis or concomitant plasma cell leukemia.

  • Pleural effusions requiring thoracentesis or ascites requiring paracentesis or any major procedures within 14 days before randomization: eg, plasmapheresis, radiotherapy, major surgery (kyphoplasty is not considered a major procedure).

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) >2.

  • Platelets <50,000 cells/μL if <50% of BM nucleated cells are plasma cells and <30,000 cells/μL if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within 3 days before the screening hematological test.

  • Absolute neutrophil count (ANC) <1000 μ/L (1 x 109/L). The use of G-CSF is not allowed to reach this level.

  • Creatinine clearance <15 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD] Formula, see Appendix B).

  • Total bilirubin >1.5 x upper limit of normal (ULN), except for known Gilbert syndrome.

  • Corrected serum calcium >14 mg/dL (>3.5 mmol/L).

  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN.

  • Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior anti-myeloma therapy of Grade >1 (National Cancer Institute Common Terminology for Adverse Events [NCI-CTCAE] v4.03.

  • Prior malignancy. Adequately treated basal cell or squamous cell skin or superficial (pTis, pTa, and pT1) bladder cancer or low risk prostate cancer or any in situ malignancy after curative therapy are allowed, as well as any other cancer for which chemotherapy has been completed ≥5 years prior to randomization and from which the patient has been disease-free for ≥5 years.

  • Any of the following within 6 months prior to randomization: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association class III or IV congestive heart failure (CHF), Grade ≥3 arrhythmias, stroke, or transient ischemic attack.

  • Left ventricular ejection fraction <40%.

  • Known acquired AIDS related illness or HIV disease requiring antiretroviral treatment, or to have hepatitis A, B, or C active infection.

  • Any of the following within 3 months prior to randomization: treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event.

  • Any severe acute or chronic medical condition which could impair the ability of the patient to participate in the study or interfere with interpretation of the study results (eg, systemic infection unless anti-infective therapy is employed), or patient unable to comply with the study procedures.

  • Female patients who are pregnant or lactating.

Étude non interventionnelle sur le monitoring du myélome multiple et de l’impact de son traitement pour des patients en première ligne de traitement éligible à l’autogreffe

Étude de phase sur le daratumumab en infusion rapide chez des patients atteints d’un myélome multiple en maladie récidivante

Critères d’inclusion:

  • Males or females, age 18 years or older.

  • ECOG performance status score of 0, 1 or 2.

  • Life expectancy of at least 3 months.

  • Measurable disease according to the IMWG criteria defined below (These baseline laboratory studies for determining eligibility must be obtained during the screening period within 28 days prior to start of study drug):

    • Serum monoclonal paraprotein (M-protein) ≥ 10 g/L (if IgG) or ≥5g/L (if IgA, D, E or M).

    • Urine M-protein ≥ 200 mg/24 h.

    • Serum free light chains (FLC) assay: Involved FLC level ≥ 100 mg/L and an abnormal serum free light chain ratio (< 0.26 or > 1.65)

  • Received at least 3 prior lines of therapy including a proteasome inhibitor (≥2 cycles or 2 months of treatment) and an IMiD (≥2 cycles or 2 months of treatment) in any order or in combination during the course of treatment) or Subjects whose disease is double refractory to a PI and an IMiD.

  • For subjects who have received more than 1 type of PI, their disease must be refractory to the most recent one. Similarly, for those who have received more than 1 type of IMID, their disease must be refractory to the most recent one.

    A single line of therapy may consist of 1 or more agents, and may include induction, hematopoietic stem cell transplantation, and maintenance therapy (refer to Appendix 2).

    Radiotherapy, bisphosphonate, or a single short course of steroids (i.e. less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy. Induction therapy followed by ASCT and consolidation/maintenance will be considered as one line. Radiotherapy, bisphosphonate, or a single short course of steroids (i.e. less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days) would not be considered prior lines of therapy.

  • Have achieved at least a minimal response (MR) or better to at least one previous line of therapy as per EBMT response criteria.
  • The following laboratory results must be met within 10 days of first study drug administration:
    • ANC ≥ 1.0 x 109/L
    • Hemoglobin ≥ 80 g/L
    • Platelets ≥ 70 x 109/L (or ≥50 x 109/L if ≥ 50% plasmacytosis in bone marrow)
    • Calculated or measured CrCl ≥ 30 mL/min
    • AST and ALT ≤ 3.0 x ULN
    • Total bilirubin ≤ 2 x ULN unless known to have Gilbert’s disease
    • Corrected serum calcium ≤ 3.5 mmol/L

Critères d’exclusion:

  • Prior exposure to daratumumab (or other anti-CD38 monoclonal antibody).

  • History of prior allogeneic stem cell transplantation and showing evidence of active graft-versushost disease or graft-versus-host disease that requires immunosuppressive therapy.

  • Chemotherapy or other anti-myeloma therapy within 14 days prior to the first dose of study drug.

  • Treatment-related toxicity that has not recovered ≤Grade 1 unless deemed to be irreversible (an example of an irreversible toxicity would include steroid induced cataracts).

  • Subjects who have received steroids within 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if subject receive ≤ 10 mg of prednisone per day, or equivalent, as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products prior to enrolment in this study.

  • Subjects who have received any investigational agents within 28 days or 5 half-lives (whichever is shorter, however the minimum allowed timeframe is 14 days) of the first dose (Cycle 1 Day 1).

  • Prior history of malignancies, other than MM, unless the subject has been free of the disease for 3 years or longer. Exceptions include the following:

    • Basal or squamous cell carcinoma of the skin

    • Carcinoma in situ of the cervix or breast

    • Adenocarcinoma of the prostate (TNM stage of T1a or T1b)

  • Other concurrent severe and/or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol.

  • Known chronic obstructive pulmonary disease (COPD), defined as a FEV1 < 50% predicted value.

  • Known moderate or severe persistent asthma within the last 2 years, or currently has uncontrolled asthma of any classification.

  • History of or current uncontrolled cardiovascular disease including:

    • Unstable angina, myocardial infarction, or known congestive heart failure Class III/IV within the preceding 12 months

    • Transient ischemic attack within the preceding 3 months, pulmonary embolism within the preceding 2 months.

    • Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third-degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy.

    • QTc prolongation as confirmed by ECG assessment at screening (QTc >470 milliseconds).

  • Known HIV positivity or active infectious hepatitis B or C.

  • Known allergies, hypersensitivity to mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to the Daratumumab IB), or known sensitivity to mammalian-derived products.

  • Known CNS involvement, amyloidosis, or currently active plasma cell leukemia.

  • Subjects who are receiving any other investigational agent.

  • Autologous, peripheral stem cell transplant within 12 weeks of the first dose of study drug.