HDS Plus PBPC Transplant Vs 4 More Courses of FrontLine Therapy in Pts With Aggressive NHL in PR After Induction Therapy

Study Overview
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Brief Summary
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The study is planned to compare the outcome of aggressive NHL patients in partial remission after four courses of front-line therapy, randomly assigned to receive either additional four courses of the same regimen or a modified HDS program.

Official Title
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A Prospective, Randomized, Multicenter Trial Comparing a Modified HDS Therapy Supported by PBPC Transplant With Additional 4 Courses of Front-Line Therapy in Adult Aggressive NHL With PR After Short Course of Up-Front Chemotherapy

Conditions
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High-Grade Lymphomas

Intervention / Treatment
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* Drug: HDS vs ProMECE/CytaBOM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed, untreated patients with histologically documented aggressive lymphoma; Age between 18 and 65 years; Clinical stage at diagnosis: I A bulky - IV B; Reduction of tumoral masses, after four courses of induction therapy, between 50 and 75%; Serum negativity for HIV, HbsAg and HCV; ECOG performance status 0 through 4; Adequate bone marrow function; Adequate renal and hepatic functions; Left ventricular ejection fraction (LVEF) > 50%; No previous malignant disease; No previous chemo-radiotherapy; No cerebral or CNS involvement, assessed by clinical history, physical examination and CSF examination through lumbar puncture; Written informed consent given at time of randomization. Exclusion Criteria: Clinical stage I no bulky, or CS IIA-B with less than three sites of disease involved; Patients with CR, unconfirmed complete remission (uCR), very good PR (>75%) and clinical response less than 50%, as defined by Cheson et al., following four courses of induction therapy; Tumor involvement of CNS (except patients with peridural masses without liquor involvement , who can be enrolled in this study); Indolent lymphoma transformed in more aggressive histologic type, even if never previously treated; Aggressive non-Hodgkin's lymphoma in pre-transplanted patient; Clinically significant secondary cardiovascular disease e.g. uncontrolled hypertension, (resting diastolic blood pressure > 115 mmHg), uncontrolled multifocal cardiac arrhythmias, symptomatic angina pectoris or congestive cardiac failure NYHA class III-IV; Left ventricular ejection fraction (LVEF) < 50%; Evidence of any severe active acute or chronic infection; Concurrent malignancy of history of other malignancy, except basal cell carcinoma of the skin (BCC) and in situ cervical carcinoma (CIN); myelodisplastic syndrome; HbsAg, HIV-positive, or HCV-RNA-positive patients; Patient with psychiatric, or any disorder that compromises ability to give truly informed consent for participation in this study; Pregnant woman; potential child-bearing women can be enrolled if adequate contraceptive precautions are used before entering this trial and for the duration of the trial; Concerns for patient's compliance with the protocol procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HDS<br>modified high dose sequential therapy | Drug: HDS vs ProMECE/CytaBOM<br> <br> |
| Active Comparator: ProMECE/CytaBOM<br>four additional courses of standard ProMECE/CytaBOM | Drug: HDS vs ProMECE/CytaBOM<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| remission duration |  | end of treatment | 
| overall survival |  | study end | 
| event-free survival |  | study end | 
| freedom-from progression |  | study end | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility and toxicity |  | end of treatment |