Study of Weekly Carfilzomib, Cyclophosphamide and Dexamethasone In Newly Diagnosed Multiple Myeloma Patients (wCCyd)

NCT01857115 | Completed Phase 1

• 1 other identifier: IST-CAR-561
• Study Type: interventional
• Target: 63
• 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 as up-front treatment in elderly Multiple Myeloma (MM) patients.

Conditions

Multiple Myeloma

Keywords

Multiple myeloma; Diagnosis; Weekly; CCyd

Outcome Measures

Primary Outcomes (2)

• Identification of Dose-limiting toxicity (DLT)

  Non-hematologic: * Grade2 neuropathy with pain * any Grade 3 toxicity (excluding nausea, vomiting, diarrhea) * Grade3 nausea, vomiting, or diarrhea despite maximal antiemetic/antidiarrheal therapy * Grade4 fatigue lasting for ≥7days * Any non-hematologic toxicity requiring a dose reduction within Cycle1 * Inability to receive Day 1 dose of Cycle2 due to drug related toxicity persisting from Cycle1 or drug related toxicity newly encountered on Day1 of Cycle2. Hematologic: * Grade 4 neutropenia (ANC\<0.5x109/L) lasting for ≥7days * Febrile neutropenia (ANC\<1.0x109/L with a fever ≥38.3ºC) * Grade 4 thrombocytopenia (platelets\<25.0x109/L) lasting ≥7 days despite dose delay * Grade 3-4 thrombocytopenia associated with bleeding * Any hematologic toxicity requiring a dose reduction within Cycle1 * Inability to receive Day1 dose of Cycle2 due to drug related toxicity persisting from Cycle1 or drug related toxicity newly encountered on Day1 of Cycle2.

  1 year

• Partial Response (PR)

  The primary efficacy endpoints will be assessed by considering partial response (PR) following the proposed regimen, at the end of third cycle.

  1 year

Secondary Outcomes (9)

• Response rate (RR)

  3 years

• Progression free-survival (PFS)

  3 years

• Time to progression (TTP)

  3 years

• Duration of response (DOR)

  3 years

• Overall survival (OS)

  3 years

Study Arms (1)

CCyd

EXPERIMENTAL

Treatment schedule for 9 cycles of induction: 1. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15. 2. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9,15-16, 22-23. 3. Carfilzomib given 20 mg/m2 IV once daily on Day 1 of Cycle 1 only followed by 36/45/56/70 mg/m2 on days 8, 15 of Cycle 1, then for all subsequent doses 70 mg/m2 IV once daily on days 1, 8, 15, followed by 14-day rest period (day 16 through 28). Treatment schedule for maintenance until progression or intolerance: Carfilzomib at the MTD defined by phase I study IV once daily on days 1, 8, 15.

Drug: Carfilzomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Interventions

Carfilzomib DRUG

Also known as: Krypolis

CCyd

Cyclophosphamide DRUG

Also known as: Endoxan

CCyd

Dexamethasone DRUG

Also known as: Decadron

CCyd

Eligibility Criteria

• Age: 65 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Disease-related
• Patient is a newly diagnosed MM patient.
• Patient is age ≥ 65 year of age or who are ineligible for autologous stem cell transplantation.
• 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.
• Demographic:
• Age ≥ 18 years.
• Life expectancy ≥ 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix F).
• Laboratory:
• Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to randomization.
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to randomization.
• Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
• Alanine transaminase (ALT): ≤ 3 x the ULN.
• Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to randomization (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines).
• Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to randomization.

You may not qualify if:

• Disease-related:
• Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; ≤ to the equivalent of dexamethasone 40 mg/day for 4 days)
• Patient with relapsed or refractory multiple myeloma.
• Patients with non-secretory MM unless serum free light chains are present and the ratio is abnormal.
• Concurrent Conditions:
• Pregnant or lactating females (Appendix I).
• Major surgery within 21 days prior to randomization.
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization.
• Known human immunodeficiency virus infection.
• Active hepatitis B or C infection.
• Unstable angina or myocardial infarction within 4 months prior to randomization, 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, uncontrolled congestive heart failure (CHF) or uncontrolled diabetes within 14 days prior to randomization.
• 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.
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).

Sponsors & Collaborators

• European Myeloma Network B.V.: lead
• Fondazione EMN Italy Onlus: collaborator

Study Sites (1)

Fondazione EMN Italy Onlus

Torino, 10126, Italy

Location

Related Publications (2)

• Mina R, Bonello F, Petrucci MT, Liberati AM, Conticello C, Ballanti S, Musto P, Olivieri A, Benevolo G, Capra A, Gilestro M, Galieni P, Cavo M, Siniscalchi A, Palumbo A, Montefusco V, Gaidano G, Omede P, Boccadoro M, Bringhen S. Carfilzomib, cyclophosphamide and dexamethasone for newly diagnosed, high-risk myeloma patients not eligible for transplant: a pooled analysis of two studies. Haematologica. 2021 Apr 1;106(4):1079-1085. doi: 10.3324/haematol.2019.243428.

  PMID: 32107329 DERIVED

• Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.

  PMID: 31221778 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Disease

Interventions

carfilzomib; Cyclophosphamide; Dexamethasone; Calcium Dobesilate

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; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

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: April 17, 2013
• First Posted: May 20, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2013
• Study Completion: September 1, 2024
• Last Updated: November 13, 2024

Record last verified: 2024-11

Locations

IT (1)