Overview

Phase I/II Study of Carfilzomib, Pomalidomide and Dexamethasone in Relapsed And/Or Refractory Multiple Myeloma Patients (CPD)

Status:
Active, not recruiting
Trial end date:
2022-06-01
Target enrollment:
0
Participant gender:
All
Summary
This protocol is a phase I/II multicenter study designed to assess the safety and the efficacy of the proposed combinations in relapsed and/or refractory Multiple Myeloma (MM) patients.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
European Myeloma Network
Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborator:
University of Turin, Italy
Treatments:
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Thalidomide
Criteria
Inclusion Criteria:

Age > 18 years. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Patient
is, in the investigator(s) opinion, willing and able to comply with the protocol
requirements.

Patient has given voluntary written informed consent before performance of any
study-related procedure not part of normal medical care, with the understanding that
consent may be withdrawn by the patient at any time without prejudice to their future
medical care.

Female patient is either post-menopausal or surgically sterilized or willing to use an
acceptable method of birth control (i.e., a hormonal contraceptive, intrauterine device,
diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the
study.

Male patient agrees to use an acceptable method for contraception (i.e., condom or
abstinence) for the duration of the study.

Patients who are primary refractory or relapsed/refractory to Lenalidomide. Subjects must
have been received at least 2 consecutive cycles of a prior treatment that include
Lenalidomide alone or in combination.

Subject must be primary refractory or relapsed/refractory to Lenalidomide, defined as: 1)
never achieved any response better than progressive disease (PD) to any
Lenalidomide-containing regimen; 2) documented disease progression during or within 60 days
of completing their last myeloma Lenalidomide-containing regimen.

Both relapsed and/or refractory to Bortezomib and naive to Bortezomib patients can be
enrolled.

Patient has measurable disease, defined as follows: any quantifiable serum monoclonal
protein value (generally, but not necessarily, ≥ 0.5 g/dL of M-protein) and, where
applicable, urine light-chain excretion of >200 mg/24 hours. For patients with oligo or
non-secretory MM, it is required that they have measurable plasmacytoma > 2 cm as
determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan) or an
abnormal free light chain ratio (n.v.: 0.26-1.65). We anticipate that less than 10% of
patients admitted to this study will be oligo- or non-secretory MM with free light chains
only in order to maximize interpretation of benefit results.

Patient has a Karnofsky performance status ≥60%. Patient has a life-expectancy >3 months.

Patient has the following laboratory values within 14 days before Baseline (day 1 of the
Cycle 1, before study drug administration):

Platelet count ≥ 50 x 109/L (≥ 30 x 109/L if myeloma involvement in the bone marrow is >
50%) within 14 days prior to drug administration).

Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (subjects may be receiving
red blood cell [RBC] transfusions in accordance with institutional guidelines).

Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors. Corrected
serum calcium ≤14 mg/dL (3.5 mmol/L) Alanine transaminase (ALT): ≤ 3.5 x the ULN. Total
bilirubin: ≤ 2 x the ULN. Calculated or measured creatinine clearance ≥ 45 mL/min.

Exclusion Criteria:

Newly diagnosed myeloma patients. Patient with non-secretory MM, unless serum free light
chains are present and the ratio is abnormal.

Pregnant or lactating females. Major surgery within 21 days prior to enrollment. Acute
active infection requiring treatment (systemic antibiotics, antivirals, or antifungals)
within 14 days prior to enrolment.

Patient has active infectious hepatitis type A, B or C or HIV. Unstable angina or
myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart
failure, uncontrolled angina, 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.

Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.

Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to
enrollment.

Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
carfilzomib).

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 pre-existing pulmonary or cardiac impairment.

Subject with pleural effusions requiring thoracentesis or ascites requiring paracentesis
within 14 days prior to baseline.

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.

Nonhematologic 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.