Outpatient Administration of R-DHAP in Relapsed/Refractory Non-Hodgkin Lymphoma

Study Overview
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Brief Summary
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The goal of this study is to evaluate the efficacy and safety of a combination of the anti-CD20 monoclonal antibody Rituximab, Dexamethasone, daily high dose Cytarabine twice, and Carboplatin; delivered in an outpatient setting.

Detailed Description
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The R-DHAP (Rituximab, Dexamethasone, Cytarabine, and Cisplatin) schedule includes high-dose cytarabine every 12 hours and requires careful monitoring of renal toxicity because of cisplatin. These conditions limit the use of this protocol in an outpatient setting. The S phase of lymphoma cells is longer than 12 hours, then cytarabine can be used daily without reduction of the antineoplastic effect. Carboplatin does not have remarkable renal toxicity so is not necessary to monitor blood chemistry or IV fluids during its administration. The study hypothesis is that modifications to the original R-DHAP protocol, using cytarabine on a daily basis and the substitution of cisplatin by carboplatin can preserve the efficacy, reducing the incidence of renal events. The investigators hypothesize that those modifications can make the schedule more suitable for an outpatient administration in relapsed or refractory non-Hodgkin lymphoma patients. After 3 cycles of chemotherapy, the overall response and the incidence of adverse events will be evaluated. In order to achieve the purpose of this trial, 130 participants will be included.

Official Title
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Safety and Efficacy of an Outpatient Schedule of Rituximab, Cytarabine, Carboplatin, and Dexamethasone in Relapsed/Refractory Non-Hodgkin Lymphoma. Phase I/II Trial.

Conditions
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Relapsed Non Hodgkin Lymphoma, Refractory Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Rituximab
* Drug: Carboplatin
* Drug: Cytarabine Injection
* Drug: Dexamethasone
* Drug: Filgrastim 0.3 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of recurrent or refractory B-cell non-Hodgkin lymphoma Performance status: Eastern Cooperative Oncology Group 0-2 At least three weeks from last chemotherapy Toxicities by Common Terminology Criteria Version 4.0 ≤ 1 Glomerular filtration rate >50 ml/min Women of childbearing potential must use effective methods of contraception Exclusion Criteria: Post-transplant relapse of lymphoma Central nervous system involvement of lymphoma Serious infections Known allergies to one or more of the experimental drugs Diabetes with glucose >200 mg/dl Pregnant or lactating females Known HIV or B Hepatitis positivity Known allergies to filgrastim

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modified DHAP<br>Rituximab 375 mg/m² day 1, i.v. Carboplatin AUC(Area Under Curve) 5 day 1, i.v. Cytarabine 2000 mg/m², on day 2 and 3, i.v. Dexamethasone 40 mg, days 1-4, i.v. Filgrastim 300 mcg, days 10-15, s.c. | Drug: Rituximab<br>* Rituximab 375 mg/m²<br>* Other names: MabThera;Drug: Carboplatin<br>* Carboplatin AUC5<br>Drug: Cytarabine Injection<br>* Cytarabine 2000 mg/m² qd 2 days<br>Drug: Dexamethasone<br>* Dexamethasone 40 mg<br>Drug: Filgrastim 0.3 MG/ML<br>* One subcutaneous injection daily for 5 days<br>* Other names: Neupogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The percentage of patients which showed either a partial remission (PR), or a complete remission (CR) after study treatment. | 63 days | 
| Incidence of hematological toxicities > grade 2 by Common Terminology Criteria V4.0 |  | 63 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 12 months | 
| Progression Free Survival |  | 12 months |