Dose Augmented Rituximab and ICE for Pts With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell NHL
Condition: Lymphoma; B-cell Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this research is to study a treatment program for patients with aggressive
      lymphoma that has come back after initial or first therapy (called relapsed) or that has not
      responded to first therapy (called refractory). Since 1993, we have used a combination of
      chemotherapy known as ICE (Ifosfamide, Carboplatin, and Etoposide) for your type of lymphoma.
      In many patients, this treatment helps the disease to shrink before giving high-dose therapy
      and autologous stem cell transplant (ASCT). Only patients who respond to these types of
      treatments have a chance of their disease going away (remission) with an ASCT. In 1999, we
      studied the same treatment but added another medicine for your type of lymphoma, Rituximab
      (Rituxan), to the ICE treatment (RICE). More patients had lymphoma shrinkage from this
      treatment (chemosensitive disease) than with ICE alone. These patients then received high
      dose therapy and autologous stem cell transplant and have an improved chance of having a
      remission.

      ICE chemotherapy is standard chemotherapy used at Memorial Sloan-Kettering Cancer Center.
      However, it is different in this study because of the higher doses. We are testing higher
      doses of RICE treatment for patients in this study.

      In our current study in Hodgkin's lymphoma, we are giving these higher doses of ICE (called
      augmented ICE) to patients who also have higher risk. We hope to show in this study that by
      using Rituximab and augmented ICE that we can improve your ability to achieve a remission
      (that is, to have the disease go away).
    

Detailed description: 
      The purpose of this study is to determine if dose escalation of the rituximab-ICE (RICEesc)
      program can improve the overall response rate of patients with primary refractory or poor
      risk relapsed aggressive B cell lymphoma. R-ICEesc will be administered for 2 cycles with
      peripheral blood progenitor cells (PBPCs) collected after cycle 2.

      A two-stage design will be employed, such that the study will be terminated if in the first
      cohort of patients it appears that the overall response rate is <50% or if >25% patients fail
      to mobilize at least 2 x 106 CD34+ cells/kg.
    

Intervention name(s): Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant
Intervention type(s): Drug
Intervention description(s): ANC must be ≥1000/µl and platelet count must be ≥50,000/µl. Rituximab will be administered at a dose of 375 mg/m2 IV on days 1 and 3 of the each cycle. Premedication will be given.ICE will be administered as follows: Day 3: Etoposide 200 mg/m2 IV q12 hrs x 3. Day 4: Ifosfamide 10 g/m2 and MESNA 10 g/m2 mixed and infused together as a continuous infusion over 48 hours. Day 5: Carboplatin IV dosed by the Calvert formula using an AUC of 5.
Carboplatin dose (mg) = 5 x (Clcr + 25) For the first ten patients enrolled, G CSF will be administered beginning on day seven of each cycle and G CSF will continue until stem cell collection is completed. The dose will be 960 ug or 10 ug/kg if weight is greater than 100 kg.
For the remaining patients, G-CSF will be administered for 10 days beginning on day 7 for cycle 1. The dose will be 300-480 ug/d. For cycle 2 the dose will be 960 ug or 10ug/kg if weight is > 100kg. Leukapheresis will continue.
Other intervention name(s): ASCT,Rituxan, Ifex, Paraplatin®, etoposide, Vepesid®, Mesnex®, Neupogen, Neulasta
Intervention MeSH terms: Rituximab; Carboplatin; Etoposide; Ifosfamide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Lymphoma; ASCT; B-cell non-Hodgkin's lymphoma; Cancer; Second line therapy; ICE; Stem cell transplant