Elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL) MedDRA version: 21.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: COLECALCIFEROLO SANDOZ
Product Name: COLECALCIFEROLO SANDOZ
Product Code: [COLECALCIFEROLO SANDOZ]
Pharmaceutical Form: Oral solution
INN or Proposed INN: COLECALCIFEROLO
CAS Number: 67-97
calcidiol, which is the form whose values are measured in the blood
calcitriol, the biologically active form of vitamin D3.
7-dehydrocholesterol is the biological precursor of vitamin D3, which is transformed into cholecalciferol after exposure to ultraviolet radiatio
Sponsors
FONDAZIONE ITALIANA LINFOMI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Histologically documented diagnosis of Diffuse Large B-cell Lymphoma or Follicular grade IIIb lymphoma, as defined in the 2017 edition of the World Health Organization (WHO) classification. 2) Age = 65 years 3) Comprehensive Geriatric Assessment (CGA) performed at baseline, before start of any treatment. 4) Eastern Cooperative Oncology Group (ECOG) performance status (PS) =3 5) Eligibility for anthracycline containing regimen (R-CHOP or R-miniCHOP) 6) No previous treatment for DLBCL or Follicular grade IIIb lymphoma 7) Ann Arbor stage I-IV 8) At least one site of measurable nodal disease at baseline = 1.5 cm in the longest transverse diameter as determined by CT scan (MRI is allowed only if CT scan cannot be performed); or one metabolic active site of disease at baseline FDG-PET scan 9) Baseline Vitamin D [25(OH)VitD] serum level = 40 ng/ml 10) Adequate hematological counts defined as follows: - Absolute Neutrophil count (ANC) > 1.5 x 109/L unless due to bone marrow involvement by lymphoma - Platelet count = 80.000/mm3 unless due to bone marrow involvement by lymphoma 11) Adequate renal function defined as follows: - Creatinine = 2 mg/dL, unless secondary to lymphoma 12) Adequate hepatic function defined as follows: - Bilirubin = 2 mg/dL unless secondary to lymphoma 13) LVEF > 50% at bidimensionally echocardiogram 14) Life expectancy = 6 months 15) Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or studyspecific procedures 16) Subject must be able to adhere to the study visit schedule and other protocol requirements 17) Men must agree to use one of the below reported acceptable method of contraception (for themselves or female partners if WOCBP) for the duration of the study and for 3 months after receiving the last dose of immunochemotherapy, and to not donate sperm while on study. Acceptable methods for birth control, to be adopted even if male is surgically sterilized (i.e., status post vasectomy) are: - practice effective barrier contraception during the entire study treatment period and through 3 months after the last dose of immunochemotherapy, or - agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods for the female partner] and withdrawal are not acceptable methods of contraception) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 430
Exclusion criteria
Exclusion criteria: 1) Histological diagnosis different from Diffuse large B-Cell Lymphoma or Follicular grade IIIb lymphoma 2) HGBL, with rearrangement of MYC, BCL2 and/or BCL6 (double-hit) 3) Use of VitD supplementation as standard of care at dose higher than 10.000 U/week (or higher than 2,000 U/day) 4) Suspect or clinical evidence of CNS involvement by lymphoma 5) Contraindication to the use of rituximab 6) Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia) 7) Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug 8) Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent 9) Any history of other active malignancies within 2 years prior to study entry, with the exception of adequately treated in situ carcinoma of the cervix uterine, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin or limited stage surgically removed breast cancer or adequately treated with radiation therapy or limited stage prostate carcinoma surgically removed or adequately treated with radiation therapy previous malignancy confined and surgically resected with curative intent 10) Evidence of other clinically significant uncontrolled condition(s) including, but not limited to: - Uncontrolled and/or active systemic infection (viral, bacterial or fungal) - Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: The purpose of this trial is to demonstrate the superiority in terms of Progression-free survival (PFS) of a prephase therapy with oral prednisone and Vitamin D supplementation versus a prephase therapy with oral prednisone alone, followed by 6 cycles of conventional immunochemotherapy, on an elderly patients population diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular lymphoma grade IIIb (FL3B).;Secondary Objective: ¿ to assess the safety of VitD supplementation in terms of hematological and extra hematological AEs rates; ¿ to evaluate the effect of VitD supplementation in terms of early mortality rate, response rate, OS, EFS; ¿ to confirm the efficacy of a prephase VitD supplementation to correct baseline 25(OH)VitD levels; ¿ to identify prognostic factors for baseline 25(OH)VitD correction; ¿ to correlate 25(OH)VitD baseline levels with known and novel prognostic biomarkers (IPI, Cell of Origin, etc.) and with activity of immunochemotherapy; ¿ to identify potential mechanisms that correlate VitD levels with activity of immunochemotherapy; ¿ to identify high risk category of individuals showing insufficient response to Vitamin D supplementation; ¿ to describe the health-related quality of life (HRQoL) by the use of Patient-Reported Outcomes (PROs): EORTC-QLQ-C30 and FACT-Lym LymS questionnaires.;Primary end point(s): Primary Endpoint: Progression-Free Survival (PFS);Timepoint(s) of evaluation of this end point: 2-year PFS. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints ¿ Overall Survival (OS) ¿ Event Free Survival (EFS) ¿ Response rate (ORR, CRR; Cheson 2014) ¿ Early mortality rate: all deaths recorded within 90 days from the date of diagnosis ¿ AEs CTCAE current version ¿ Rate of ECOG changes after prephase ¿ Rate of 25(OH)VitD correction (VitD supplementation arm): number of patients with 25(OH)VitD levels above or equal 20ng/ml at day 1 of cycle 2 ¿ Rate of patients who maintain 25(OH)VitD levels in the normal range at cycle 6 ¿ PRO endpoints include: time-to-deterioration in EORTC QLQ-C30 physical functioning and fatigue and FACT-Lym LymS; proportion of patients in each arm achieving meaningful improvement in EORTC QLQ-C30 physical functioning and fatigue, and FACT-Lym LymS; and a comparison of EORTC QLQ-C30 treatment-related symptoms between the two treatment arms.;Timepoint(s) of evaluation of this end point: The best overall response will be defined as the best response between the date of beginning of therapy and the last restaging. Patients without response assessment (due to whatever reason) will be considered as non-responders. Patients who will interrupt therapy (for any reason) will be followed for survival up to 12 months after treatment discontinuation. | — |
Countries
Italy
Contacts
Public ContactUffici studi FIL - area startup
Fondazione Italiana Linfomi Onlus
Outcome results
None listed