2024-511637-35-00RecruitingPhase 3
Prephase treatment with prednisone +/- Vitamin D supplementation followed by immunochemotherapy in Elderly patients with Diffuse Large B-Cell Lymphoma (DLBCL). A randomized, open label, phase III study by Fondazione Italiana Linfomi.
Fondazione Italiana Linfomi Ets43 sites in 1 country430 target enrollmentStarted: November 18, 2024Last updated:
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Enrollment
- 430
- Locations
- 43
- Primary Endpoint
- Progression-Free Survival (PFS).
Study Overview
Brief Summary
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).
Eligibility Criteria
- Ages
- 65 years to 65+ years (65+ Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •Adequate hematological counts defined as follows: - Absolute Neutrophil count (ANC) > 1.5 x 10^9/L unless due to bone marrow involvement by lymphoma - Platelet count ≥ 80.000/mm3 unless due to bone marrow involvement by lymphoma
- •Adequate renal function defined as follows: - Creatinine ≤ 2 mg/dL, unless secondary to lymphoma
- •Adequate hepatic function defined as follows: - Bilirubin ≤ 2 mg/dL unless secondary to lymphoma
- •LVEF > 40% at bidimensionally echocardiogram
- •Life expectancy ≥ 6 months
- •Subject understands and voluntarily signs an informed consent form approved by an Independent Ethics Committee (IEC), prior to the initiation of any screening or study-specific procedures
- •Subject must be able to adhere to the study visit schedule and other protocol requirements
- •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)
- •Age ≥ 65 years
- •Simplified Geriatric Assessment (sGA) performed at baseline, before start of any treatment.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤3
- •Eligibility for 6 cycle treatment of anthracycline containing regimen (R-CHOP or R-miniCHOP)
- •No previous treatment for DLBCL or Follicular grade IIIb lymphoma
- •Ann Arbor stage I-IV
- •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
- •Baseline Vitamin D [25(OH)VitD] serum level ≤ 40 ng/ml
Exclusion Criteria
- •Histological diagnosis different from Diffuse large B-Cell Lymphoma or Follicular grade IIIb lymphoma, including diagnosis of HGBL, with rearrangement of MYC, BCL2 and/or BCL6 (double-hit)
- •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.
- •Use of VitD supplementation as standard of care at dose higher than 10,000 U/week (or higher than 2,000 U/day).
- •Suspect or clinical evidence of CNS involvement by lymphoma.
- •Contraindication to the use of rituximab.
- •Localized stage patients candidates for 3-4 cycles of R-CHOP/R-miniCHOP +RT.
- •Contraindication to the use of VitD supplementation (Hypercalcemia/Hyperphosphatemia).
- •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.
- •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.
- •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 or previous malignancy confined and surgically resected with curative intent.
Outcomes
Primary Outcomes
Progression-Free Survival (PFS).
Progression-Free Survival (PFS).
Secondary Outcomes
- Event Free Survival (EFS).
- Overall Survival (OS).
- Response rate (ORR, CRR; Cheson 2014).
- Early death rate (EDR): all deaths recorded within 90 days from the date of diagnosis.
- AEs rate (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 EOI.
- PROs 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.
Investigators
Francesco Merli, MD
Scientific
Fondazione Italiana Linfomi Ets
Study Sites (43)
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