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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02955823
Recruitment Status : Active, not recruiting
First Posted : November 4, 2016
Last Update Posted : May 27, 2022
Sponsor:
Information provided by (Responsible Party):
Fondazione Italiana Linfomi ONLUS

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cells Non-Hodgkin Lymphoma Drug: Rituximab-Dexamethasone-Lenalidomide Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Study Start Date : September 2016
Actual Primary Completion Date : September 22, 2020
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: 1 arm for all patient: Ritux-Dexame-Lena
Rituximab-Dexamethasone-Lenalidomide
Drug: Rituximab-Dexamethasone-Lenalidomide
  1. 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
  2. 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 Outcome Measures :
  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 Outcome Measures :
  1. CR [ Time Frame: 48 months ]
    1) Complete response rate (CR) according to Response Criteria for non-Hodgkin lymphoma (NHL) with CT scan; Cheson 2014.

  2. OS [ Time Frame: 54 months ]
    2) 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 ]

    3) 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 ]
    4) 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 ]
    5) 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.



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Ages Eligible for Study:   70 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically proven CD20 positive Diffuse Large B-cell Lymphoma according to WHO classification (local pathologist)
  2. Age ≥ 70 years
  3. Previously untreated
  4. CGA assessment performed before starting treatment
  5. 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

  6. Ann Arbor Stage I - IV (Appendix F)
  7. At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
  8. ECOG performance status of 0- 3 (Appendix E)
  9. No active hepatitis C virus (HCV) infection. In case of HCV positivity HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
  10. 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
  11. Ability and willingness to comply with the study protocol procedure
  12. Life expectancy > 6 months
  13. Patients must give written informed consent.
  14. 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:

  1. Histological diagnosis different from CD20 positive Diffuse Large B-cell Lymphoma are excluded.
  2. Previous exposure to cytotoxic agents
  3. Suspect or clinical evidence of CNS involvement by lymphoma
  4. Contraindication to the use of Rituximab or of Lenalidomide
  5. 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.
  6. HIV positivity
  7. Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir.
  8. 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
  9. AST /ALT > 2 x UNL; bilirubin > 2 x UNL; serum creatinine > 2.5 mg /dL
  10. Creatinine clearance < 10 mL/min
  11. Evidence of any severe active acute or chronic infection
  12. Severe cardiac dysfunction (NYHA grade III-IV)
  13. Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
  14. Absence of caregivers in non-autonomous patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02955823


Locations
Show Show 18 study locations
Sponsors and Collaborators
Fondazione Italiana Linfomi ONLUS
Investigators
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Principal Investigator: Guido Gini, MD Clinica di Ematologia A.O.Universitaria Ospedali Riuniti, Ancona
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Responsible Party: Fondazione Italiana Linfomi ONLUS
ClinicalTrials.gov Identifier: NCT02955823    
Other Study ID Numbers: FIL_ReRi
First Posted: November 4, 2016    Key Record Dates
Last Update Posted: May 27, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Fondazione Italiana Linfomi ONLUS:
B cell Lymphoma
non-Hodgkin Lymphoma
Elderly patients
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Rituximab
Lenalidomide
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors