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NCT Number: NCT02955823

A Phase II Study of the FIL on Elderly Frail Patients With DLBCL

A phase II study to evaluate the combination of Lenalidomide and Rituximab as front line therapy for the treatment of elderly frail patients evaluated in CGA with Diffuse Large B-cells non-Hodgkin Lymphoma.

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Key information

Conditions

Diffuse Large B-cells Non-Hodgkin Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

70 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) - Ematologia, Meldola, Forlì-Cesena, Italy

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About this study

This is a prospective, multicenter, single arm, phase II trial in elderly patients (≥ 70 years) affected by DLBCL defined as frail according to CGA and previously untreated.

The primary endpoint is to evaluate the efficacy of the R2 (Revlimid+Rituximab) combination in first line DLBCL patients not candidate for the standard R-CHOP (or R-CHOP like) treatments due to the frail status.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
  • Age ≥ 70 years
  • Previously untreated
  • CGA assessment performed before starting treatment
  • FRAIL patients defined as follows

Age > 80 years (with UNFIT profile):

ADL ≥ 5 residual functions and/or IADL ≥ 6 residual functions and/or CIRS: 0 comorbidity of grade 3-4 and 5-8 comorbidities of grade 2

Age < 80 (ONLY one of the following criteria):

ADL ≤ 4 residual functions IADL ≤ 5 residual functions CIRS: 1 comorbidity of grade 3-4 or > 8 comorbidities of grade 2

  • Ann Arbor Stage I - IV (Appendix F)
  • At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
  • ECOG performance status of 0- 3 (Appendix E)
  • No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
  • Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:
  • Hemoglobin > 10 g/dL
  • WBC > 2500/mmc with PMN > 1000/ mmc
  • Platelets count ≥ 75000/mmc
  • Creatinine clearance ≥ 10 mL/min
  • Ability and willingness to comply with the study protocol procedure
  • Life expectancy > 6 months
  • Patients must give written informed consent.
  • Male subjects must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following investigational product discontinuation, even if he has undergone a successful vasectomy.

Exclusion criteria

  • Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
  • Previous exposure to cytotoxic agents
  • Suspect or clinical evidence of CNS involvement by lymphoma
  • Contraindication to the use of Rituximab or of Lenalidomide
  • HBsAg positivity; HBsAg-negative patients with anti-HBc antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and antiviral treatment with Lamivudine or Tenofir is provided.
  • HIV positivity
  • Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
  • Any history of other malignancies within 5 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
  • AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL
  • Creatinine clearance < 10 mL/min
  • Evidence of any severe active acute or chronic infection
  • Severe cardiac dysfunction (NYHA grade III-IV)
  • Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
  • Absence of caregivers in non-autonomous patients

Treatment and study plan

Rituximab-Dexamethasone-Lenalidomide

Drug
  • st CYCLE: Rituximab 375 mg/m2 i.v. on days 1,8,15; Dexamethasone 5 mg p.o. on days 1,8,15,22; Lenalidomide 15 mg/day p.o. day 2-22
  • nd-4th CYCLE: Rituximab 375 mg/m2 i.v. on day 1; Lenalidomide 20 mg/day p.o. from day 2 to day 22 At the end of 4th CYCLE disease restaging: - if ≥ PR continues with the 5th and 6th cycle: Rituximab 375 mg/m2 i.v. on day 1, Lenalidomide 20 mg /day p.o. day 2-22
  • if <PR stops the treatment, only follow-up At the end of the 6th CYCLE disease restaging: - if ≥ PR continues with beyond the 6th cycle with Lenalidomide 10mg dd1-21q28 until cycle 12th
  • if <PR stops the treatment, only follow-up Then, accordingly response rate after the sixth cycle assessment(≥ PR) lenalidomide will be continued at 10 mg dd1-21q28 until 12th cycle or unacceptable toxicity.

Primary outcomes

  1. ORR

    Time frame: 48 months

    Overall response rate (ORR) is defined as the proportion of patients with complete and partial response respectively according to Cheson 2014 (Appendix K).

    The ORR rate will be evaluated both on assessed patients and on all treated patients, considering patients without a response assessment (due to any reason) as non-responders.

    Response of R2 will be calculated for the EP according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014; patients will be categorized into Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Non Responders (NR).

  2. Safety: clinical relevant toxicity

    Time frame: 48 months

    Clinical relevant toxicity, defined as the proportion of patients experiencing a grade 3 or greater non haematological toxicity.

Secondary outcomes

  1. CR

    Time frame: 48 months

    • Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.

  2. OS

    Time frame: 54 months

    • Overall Survival (OS) will be defined as the time between the date of enrolment and the date of death from any cause. Patients who have not died at the time of the final analysis and patients who are lost to follow up will be censored at the date of the last contact.

  3. PFS

    Time frame: 54 months

    • Progression Free Survival (PFS) will be defined as the time between the date of enrolment and the date of disease progression, relapse or death from any cause. Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date.

    Time to event data (PFS, OS) will be estimated using the Kaplan-Meier method. The curves will be plotted and the 95% confidence interval for median time will be calculated.

  4. EFS

    Time frame: 54 months

    • Event-Free Survival (EFS), (time to treatment failure) is measured from the time from study entry to any treatment failure including disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death). Responding patients, patients who are lost to follow up, who withdrawal the consent or drop-out due to adverse event will be censored at their last assessment date. Patients died due to tumor will be considered in progression. Patients died for any other cause will be censored to the death date.

  5. Quality of life

    Time frame: 54 months

    • Patients will assess their health-related quality of life (HRQoL) using two validated questionnaires: the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) and the Quality of life (EORTC-QLQ-C30). Items for inclusion in the lymphoma subscale were selected on the basis of symptom relevance, disease specificity, and clinical relevance.

Sponsors and collaborators

Lead sponsor

Fondazione Italiana Linfomi - ETS

Other

Registry information

Official study title

A Combination of Lenalidomide and Rituximab as Front Line Therapy for the Treatment of Elderly Frail Patients Evaluated in CGA With Diffuse Large B-cells Non-Hodgkin Lymphoma. A Phase II Study of the Fondazione Italiana Linfomi (FIL)

Important dates

Study start
2016
Primary completion
2020
Study completion
2022
First posted
Nov 4, 2016
Registry last updated
Dec 23, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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