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

NCT02185820 | Completed Phase 1 DMC

• 1 other identifier: EMN07/IST-CAR-538
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; Relapsed and/or refractory; CPD

Outcome Measures

Primary Outcomes (2)

• DLT

  The dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of carfilzomib, pomalidomide and dexamethasone (CPd) association.

  1 year

• Partial response

  Determine the rate of partial response (PR) with the CPd association: a PR rate of 25% (p0) is considered not promising (H0) and a 45% (p1) as interesting.

  3 years

Secondary Outcomes (8)

• Toxicities

  3 years

• PFS

  3 years

• TTP

  3 years

• DFS

  3 years

• DOR

  3 years

Study Arms (1)

1

EXPERIMENTAL

Treatment schedule for 8 cycles of induction: Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27/36/45/56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 27/36/45/56 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Treatment schedule for maintenance until progression or intolerance: Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days cycles. Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22.

Drug: Carfilzomib; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

1

Pomalidomide DRUG

1

Dexamethasone DRUG

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Myeloma Network B.V.: lead
• University of Turin, Italy: collaborator

Study Sites (1)

Dipartimento di Biotecnologie Molecolari e Scienze per la Salute

Torino, 10126, Italy

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Sara Bringhen, MD

  A.O.U. Città della Salute e della Scienza

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 10, 2014
• Study Start: June 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: January 1, 2023
• Last Updated: July 3, 2023

Record last verified: 2023-06

Locations

IT (1)