Patients with B-cell NHL that comes back after chemotherapy are typically treated with cisplatin, high-dose cytosine arabinoside and dexamethasone (DHAP) or other platinum-based treatments. Recent studies have shown a 37% response rate in patients with large cell lymphoma to immunotherapy with Rituxan. Patients <75 years old and in otherwise good health may be candidates for high dose therapy with stem cell rescue if they have disease that remains sensitive to chemotherapy. Typically, patients are administered 2 cycles of DHAP or ICE (ifosfamide, carboplatin, and etoposide) and, if the disease responds, they proceed to high-dose therapy with stem cell support. Even patients not considered transplant candidates are also often treated with DHAP or ICE or other salvage regimens. It is likely that the response rate with DHAP alone in patients eligible for transplant is <59%. Recent studies have attempted to improve on the results from DHAP or ICE by combining them with rituxan. NCCTG has just completed a phase II trial of R-DHAP. Preliminary results of the R-ICE protocol indicate a higher response rate and longer time to progression than traditional ICE.
The problem with DHAP and ICE is that they are associated with significant side effects and specifically, with DHAP the cisplatin often causes kidney problems. In fact, some patients who are considered transplant eligible before DHAP may become transplant ineligible simply by the kidney side effects. Clearly, there is a need to improve the quality of life of patients undergoing treatment and to avoid the kidney problems.
- Patients with any stage (I-IV, including those with bone marrow involvement) relapsed CD20+ B-cell non-Hodgkins lymphoma, within 5 years, with aggressive histology who have not responded to, or relapsed after, initial chemotherapy and would, if treated off-study, be treated with a platinum-containing regimen.
- CD20+ diffuse large cell, mantle cell, or transformed histologies are eligible.
- Tumor biopsy to demonstrate histology < = 6 weeks prior to registration. Computed tomography (CT) or ultrasound guided needle biopsies are acceptable as long as the pathologists can confirm histology and the CD20 positivity of the tumor.
- Measurable disease (to be considered measurable the lesion must be greater than or equal to 1.5 x 1.5 cm).
- Greater than or equal to 18 years of age.
- ECOG performance status (PS) 0, 1, or 2.
- Limited to one prior chemotherapy regimen. Antibody therapy alone or immunotherapy alone will not count as a prior regimen - only chemotherapy regimens (for example - RCHOP, CVP, etc.). External beam radiation therapy does not count as a regimen.
- The following laboratory values obtained less than or equal to 14 days prior to registration:
- Absolute neutrophil count (ANC) greater than or equal to 1500
- Platelets (PLT) greater than or equal to 75,000
- Total bilirubin less than or equal to 2 mg/dL
- Creatinine less than or equal to 1.5 x upper normal limit (UNL)
- Any of the following as this regimen may be harmful to a developing fetus or nursing child:
- Pregnant women
- Nursing women
- Women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
- HIV infection.
- Prior chemotherapy or biologic therapy <= 4 weeks prior to registration .
- Persistent acute toxicities due to prior chemotherapy or biologic therapy.
- Active malignancies other than NHL.
- Central nervous system (CNS) lymphoma.
- Any of the following comorbid conditions:
- Uncontrolled diabetes mellitus
- Uncontrolled hypertension
- Uncontrolled peptic ulcer disease
- Uncontrolled infection
If patients take part in this study, they will get Rituximab through a needle into a vein in their arm over several hours once a week for four weeks. Patients don't usually need to be admitted to the hospital to get this treatment. The ROAD chemotherapy will be given once every three weeks for two treatments. For this treatment the patient will either receive it in a chemotherapy outpatient center or they may enter the hospital because of the timing of administration of the chemotherapy. After the oxaliplatin is finished, the patient will be given one dose of cytosine arabinoside followed by a second dose the following day. Each dose will be given by vein over several hours. The third drug, dexamethasone, is given either by mouth or by vein for four days. If hospitalized, patients may be in the hospital for 2-3 days for the chemotherapy and the last day of dexamethasone may be given by mouth as an outpatient. The day after the cytosine arabinoside is finished and before the patient leaves the hospital, they will be administered a long-acting granulocyte-colony stimulating factor (pegfilgrastim). Pegfilgrastim is a drug that is given under the skin once per cycle of chemotherapy to shorten the number of days that a patient's white blood cell count is low and therefore lower the risk of an infection. Three weeks after the first dose of ROAD (right
before the second dose) the patient's lymphoma will be checked to make sure that the lymphoma is responding to this treatment program. Patients will then get the second dose of ROAD and return 4 weeks later for testing. At this point they will have finished this treatment program and they will be told if the disease has responded. Further treatment after this point will be decided by their doctor.
Patients will be in the study for five years.Sponsor(s): Mayo Cancer Center Research Consortium (MCCRC)
Last updated: 04/18/2011
NCT ID: NCT00166439