Phase II of High-dose Therapy in Elderly Patients With Relapsed Aggressive NHL or Resistant to First Line Therapy

Study Overview
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Brief Summary
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A phase II prospective, non-randomized study. The study aim is to evaluate the feasibility and activity of high-dose therapy with stem cell in elderly patients with aggressive lymphoma relapsed FIT or resistant to first line therapy.

Detailed Description
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The study aim is to evaluate the toxicity and activity of a therapeutic approach to high doses with support of peripheral blood stem cells (PBSC) in patients aged ≥ 65 and ≤75 years, chemosensitive relapsed or refractory to therapy first line in terms of event free survival (EFS) and treatment related mortality (TRM)

Official Title
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A Phase II Prospective Study of High-dose Myeloablative Therapy, With Stem Cell Devices Support in Elderly Patients (≥65 and ≤ 75 Years) With Relapsed Aggressive Non-Hodgkin Lymphoma or Resistant to First Line Therapy

Conditions
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Non Hodgkin Lymphoma

Intervention / Treatment
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* Drug: R-DHAP/R-ICE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of NHL relapse and refractory pts age ≥ 65 and ≤75 ECOG performance status <2 FIT patients (Instrumental Activity of Daily Living (IADL)=8, Activity of Daily Living (ADL)=6, Cumulative Illness Rating Scale (CIRS) =0 SCORE=3-4, <5 SCORE=2 ) evaluable disease no RT since 3 week absolute neutrophil count >= 1500/mm3 and platelets >= 100.000/106L Creatinin <= 1.5 mg/dL and clearance >40 ml/min/24 h bilirubins < =2 mg/dL forced expiratory volume >50% - arterial pressure O2 >70 mmHg no other neoplastic disease Life expectancy> 3 months signed informed consent Exclusion Criteria: HBV+ - HCV+ - HIV+ NSC involvement - medullar infiltration > 20% other chemotherapy or radiotherapy cardiac disease alteration of liver and kidney function infections demented patient no compliance and depressed pts Frail and Unfit pts

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-DHAP/R-ICE<br>High-dose myeloablative therapy (R-DHAP or R-ICE) and conditioning therapy (BEAM or FEAM) in elderly patients with relapsed NHL or resistant to firs line therapy | Drug: R-DHAP/R-ICE<br>* R-DHAP/R-ICE 3 cycles every 21 days: R-DHAP Rituximab 375 mg/m2, e.v. day 1 Desamethasone 40 mg days 1-4 cis-Platino100 mg/m2, day 2 (if ≥70 years 75 mg/m2) Aracytin 2000 mg/m2, e.v. day 3 (if ≥70 years 1500 mg/m2) R-ICE Rituximab 375 mg/m2, e.v. day 1 Etoposide 100 mg/mq, e.v. days 1,2,3 (if ≥70 years 75 mg/mq) Ifosfamide with Mesna equidone 5000 mg/mq, day 2 (if ≥70 years 3750 mg/mq) Carboplatino AUC=5, e.v. (max 800 mg/mq), day 2 (if ≥70 years AUC=4) Conditioning BEAM or FEAM<br>* Other names: R-DHAP or R-ICE and BEAM or FEAM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event free survival EFS | Evaluate the toxicity and activity of a therapeutic approach to high doses with stem cell support device (PBSC) in patients aged ≥ 65 and ≤75 years, chemosensitive relapsed or refractory to 1st line therapy in terms of EFS. | 36 months | 
| Treatment related mortality TRM | Evaluate the toxicity and activity of a therapeutic approach to high doses with stem cell support device (PBSC) in patients aged ≥ 65 and ≤75 years, chemosensitive relapsed or refractory to 1st line therapy in terms of TRM. | 100 days from the high doses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission (CR) rate |  | 48 months (at the end of therapy) | 
| Overall Survival (OS) |  | 48 months (at the end of therapy) | 
| Adverse events incidence evaluation (grade III or IV) | Number of participants with adverse events (grade III or IV) | 48 months (at the end of therapy) | 
| Quality of Life (QoL) | Evaluate the quality of life (QoL) before, after therapy rescue and after six months of high-dose therapy through the quality of life questionnaire of European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) | 54 months | 
| Immunologic evaluation | Rating basic immunology and 6 months after therapy high doses (lymphocyte subpopulations and Ig subclasses) | 54 months |