Overview

Isa-KRd vs KRd in Newly Diagnosed Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplantation (IsKia TRIAL)

Status:
Recruiting
Trial end date:
2032-12-31
Target enrollment:
0
Participant gender:
All
Summary
This protocol is a phase III study designed to compare the efficacy and the safety of Isa-KRd induction, transplant, Isa-KRd post ASCT consolidation and Isa-KRd light consolidation vs KRd induction, transplant, KRd post ASCT consolidation and KRd light consolidation After confirmation of eligibility criteria patients will be randomized to one of the 2 treatment groups in a 1:1 randomization ratio.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
European Myeloma Network
Collaborators:
Amgen
EMN Research Italy
Sanofi
Treatments:
BB 1101
Dexamethasone
Dexamethasone acetate
Lenalidomide
Criteria
Inclusion Criteria:

- Patient with newly diagnosed multiple myeloma and eligible to ASCT.

- Patient is, in the investigator's opinion, willing and able to comply with the study
visits and procedures required per protocol.

- Patient has provided written informed consent in accordance with federal, local, and
institutional guidelines prior to initiation of any study-specific activities or
procedures. Subject does not have kind of condition that, in the opinion of the
Investigator, may compromise the ability of the subject to give written informed
consent and patient is, in the investigator(s) opinion, willing and able to comply
with the protocol requirements.

- Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven
plasmacytoma and documented multiple myeloma satisfying at least one of the calcium,
renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:

- CRAB criteria:

- Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than upper limit of
normal (ULN) or >2.75 mmol/L (>11 mg/dL)

- Renal insufficiency: creatinine clearance <40mL/min or serum creatinine >177
μmol/L (>2 mg/dL)

- 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

- Biomarkers of Malignancy:

- Clonal bone marrow plasma cell percentage ≥60%

- Involved: uninvolved serum FLC ratio ≥100

- >1 focal lesion on magnetic resonance imaging (MRI) studies

- Patient is 18 - 70 years old and is eligible for autologous stem cell transplantation

- Patient has measurable disease as defined by any one of the following:

- Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level
≥200 mg/24 hours; or

- Light chain multiple myeloma without measurable disease in the serum or the
urine: Serum immunoglobulin FLC ≥10 mg/dL and abnormal serum immunoglobulin kappa
lambda FLC ratio.

- Life expectancy ≥ 3 months

- ECOG status ≤2

- Clinical laboratory values meeting the following criteria during the Screening Phase:

- Adequate hepatic function, with serum (alanine aminotransferase) ALT ≤ 2.5 times
the upper limit of normal (ULN), AST (aspartate transaminase) ≤ 2.5 x the ULN

- Serum direct bilirubin ≤ 1.5 ULN) (except in subjects with congenital
bilirubinemia, such as Gilbert syndrome, direct bilirubinemia ≤ 1.5 ULN)

- Absolute neutrophil count (ANC) ≥ 1.0 × 109/L

- Platelet count ≥ 75× 109/L (≥ 50× 109/L if myeloma involvement in the bone marrow
is > 50%) and no platelet infusion in the 1 week prior to screening platelet
count

- Creatinine clearance (CrCl) ≥ 30 mL/minute. Creatinine clearance should be
calculated using eGFR (Modified Diet in Renal Disese [MDRD])

- Corrected serum calcium ≤ 13.5 mg/dL (3.4 mmol/L)

- LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of
evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not
available.

- Females of childbearing potential (FCBP)* complies with the conditions of the
Pregnancy Prevention Plan, including confirmation that she has an adequate level of
understanding and must agree to ongoing pregnancy testing and to practice
contraception or true abstinence. FCBP must use a highly effective and an additional
barrier contraception method simultaneously for 4 weeks before starting therapy,
during treatment and dose interruptions and for 5 months after the last dose of study
drugs.

- Male subjects must agree to practice contraception if sexually active with FCBP during
the treatment and for 5 months after the last dose of study drugs. Males must agree to
refrain from donating sperm for at least 90 days after the last dose of carfilzomib
and for at least 5 months after the last dose of isatuximab.

- *Note 1: a FCBP is a woman who:

- has achieved menarche at some time point,

- has not undergone a hysterectomy or bilateral oophorectomy or,

- has not been naturally postmenopausal (amenorrhea following cancer therapy does not
rule out childbearing potential) for at least 24 consecutive months (ie, has had
menses at any time in the preceding 24 consecutive months).

- Note 2: true abstinence is acceptable when this is in line with the preferred and
usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation,
symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of
contraception.

Exclusion Criteria:

- Previous treatment with anti-myeloma therapy (does not include radiotherapy,
biphosphonates, or a single short course of steroid ≤ to the equivalent of
dexamethasone 40 mg/day for 4 days).

- Patients with non-secretory MM unless serum free light chains are present and the
ratio is abnormal or a plasmacytoma with minimum largest diameters of > 2 cm.

- Patients with plasma cell leukemia, amyloidosis, Waldenstrom Disease, POEMS syndrome

- Meningeal involvement of multiple myeloma

- Patient ineligible for autologous transplantation

- Pregnant or lactating females

- Acute active infection requiring treatment (systemic antibiotics, antivirals, or
antifungals) within 14 days prior to randomization

- Known human immunodeficiency virus infection (HIV)

- Active hepatitis A, B or C infection. Hepatitis C infection (subjects with hepatitis C
that achieve a sustained virologic response after antiviral therapy are allowed), or
hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that
achieve sustained virologic response with antiviral therapy are allowed). Tests to be
performed if required per local country regulations. In fact it is not possible to
avoid the risk of virological reactivation with the study treatments.

- Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA
Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension,
(Uncontrolled hypertension, defined as an average systolic blood pressure ≥ 160 mmHg
or diastolic ≥ 100 mmHg despite optimal treatment (measured following European Society
of Hypertension/European Society of Cardiology 2013 guidelines), pulmonary embolia,
history of severe coronary artery disease, severe uncontrolled ventricular
arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia
or Grade 3 conduction system abnormalities unless subject has a pacemaker

- Non-hematologic malignancy within the past 3 years with the exception of a) adequately
treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b)
carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or
less with stable prostate-specific antigen levels; or d) cancer considered cured by
surgical resection or unlikely to impact survival during the duration of the study,
such as localized transitional cell carcinoma of the bladder or benign tumors of the
adrenal or pancreas

- Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
randomization as defined by National Cancer Institute Common Toxicity Criteria (NCI
CTCAE) 5.0

- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
carfilzomib) and to PS80; prior hypersensitivity to sucrose, histidine (as base and
hydrochloride salt), or any of the components (active substance or excipients) of
study treatments that are not amenable to premedication with steroids, or H2 blockers,
that would prohibit further treatment with these agents.

- Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to all anticoagulation and antiplatelet options, antiviral
drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment

- Any other clinically significant medical disease or condition that, in the
Investigator's opinion, may interfere with protocol adherence or a subject's ability
to give informed consent

- Pregnant or breastfeeding woman or woman who intends to become pregnant during the
participation in the study. FCBP unwilling to prevent pregnancy by the use of 2
reliable methods of contraception for ≥4 weeks before the start of study treatment,
during treatment (including dose interruptions), and for at least 28 days following
discontinuation of study lenalidomide, or 30 days following discontinuation of
carfilzomib or for 5 months after discontinuation of isatuximab treatment, whichever
occurs last,

- Male participants who disagree to practice true abstinence or disagree to use a condom
during sexual contact with a pregnant woman or a FCBP while participating in the
study, during dose interruptions, and for at least 28 days following discontinuation
of study lenalidomide, or 30 days following discontinuation of carfilzomib, or for 5
months after discontinuation of isatuximab treatment, whichever occurs last, even if
he has undergone a successful vasectomy.