IFM 2020-01 (Isamyp) Efficacity assessment of isatuximab plus pomalidomide and dexamethasone in patients with AL amyloidosis who didn't reach at least a very good partial response with their previous treatment

Korábbi kezelés

• Active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (i.e acute leukemia) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy
• Known positive for HIV or active hepatitis A, B or C: • Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA Of note: Patient can be eligible if anti-HBc IgG positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. o If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period. Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met. • Active HCV infection: positive HCV RNA and negative anti-HCV. Of note: Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible
• Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior therapy > G1 (NCI-CTCAE v5.0)

Más betegség

• NT-proBNP > 8500 ng/L and hs-troponin I > 100 ng/L or hs-troponin T > 50 ng/L (cardiac stage IIIb patients)
• Repetitive ventricular arrhythmias on 24h Holter ECG despite anti‐arrhythmic treatment sustained ventricular tachycardia, aborted ventricular fibrillation, atrioventricular nodal or sinoatrial nodal dysfunction with no pacemaker
• Chronic atrial fibrillation with uncontrolled heart rate
• Significant cardiac dysfunction; myocardial infarction within 12 months; unstable poorly controlled angina pectoris
• Uncorrected valvular disease unrelated to AL amyloid cardiomyopathy
• History of malignancy (other than AL amyloidosis) within 3 years before the date of inclusion (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)
• Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results

Laborértékek

• QT interval as corrected by Fridericia’s formula > 550 msec without pacemaker,
• Previous anti-CD38 therapy < 1 year before the C1D1 or Pomalidomide therapy (if refractory to Pomalidomide and/or anti-CD38 therapy)
  • Hypersensitivity to IMiD® or anti-CD38 defined as any hypersensitivity reaction leading to stop IMiD® or anti-CD38 within the 2 first cycles or toxicity, which does meet intolerance definition
  • Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, polysorbate 80, poloxamer 188, sucrose or any of the other components of study treatment that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
  • AL amyloidosis with isolated soft tissue involvement
  • Bone marrow plasma cells >30% or symptomatic multiple myeloma

Egyéb

• Presence of non-AL amyloidosis
• Undergoing dialysis
• Pregnant or breast-feeding females
• Supine systolic blood pressure < 90 mmHg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of < 80 mmHg despite medical management (i.e. midodrine, fludrocortisones) in the absence of volume depletion

• Age ≥ 18
• Male participants must agree to use contraception during the intervention period and for at least 5 months after the last dose of IsaPd and refrain from donating sperm during this period. Female participants are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: - Not a Female of childbearing potential (FCBP), OR a FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment and must either commit to continue complete abstinence from heterosexual intercourse or apply two reliable methods of birth control (One highly effective method and one additional effective method) used at the same time, beginning 4 weeks before initiation of treatment, during the intervention period and for at least 5 months after IsaPd treatment, Serum pregnancy test must be performed for all women of childbearing potential within 24 hours prior to the start of the treatment, weekly for the first 28 days of treatment and then, every 28 days while on treatment, during dose interruption, then at study discontinuation and at day 28 after end of treatment. In addition, a pregnancy test may be done at any time during the study at the discretion of the investigator if a subject misses a period or has unusual menstrual bleeding.
• 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.
• Histologic diagnosis of AL amyloidosis;
• Patients should have received at least one line with an alkylating agent and/or a PI, and/or with an anti-CD38 which the last administration ≥ 1 year before the C1D1 and dexamethasone and not be in VGPR (or better) at the time of inclusion (patients who did not reach VGPR before, or patients in VGPR or better before but with a hematological relapse at the time of inclusion can be included);
• Measurable hematologic disease: difference between involved and uninvolved FLC > 50 mg/L with an abnormal k/l ratio;
• Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system)
• Wash‐out period of at least 4 weeks from previous antitumor therapy or any investigational treatment or 5 half‐lives from previous antibodies, whichever is longer.
• Adequate bone marrow function prior to 1st drug intake (C1D1), without transfusion or growth factor support within 5 days prior to 1st drug intake, defined as: - Absolute neutrophils count ≥ 1000/mm3, - Platelets ≥ 75000/mm3, - Hemoglobin ≥ 8.0 g/dL,
• Adequate organ function defined as: - Serum ASAT and ALAT ≤ 3.0 X Upper Limit of the normal range (ULN), - Serum total bilirubin level < 1.5 x ULN, unless for subjects with Gilbert’s syndrome where the direct bilirubin should then be ≤ 2.0 x ULN.
• ECOG status ≤ 2