Trial of Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD) in Patients With Relapsed Non-Hodgkins Lymphoma

Mayo Clinic

Status and phase: Completed; Phase 2

Conditions: Lymphoma

Treatments: Drug: Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD)

Study type: Interventional

Funder types: Other

Identifiers

NCT00166439

2328-04 (Other Identifier)

MC0485 (Other Identifier)

Details and patient eligibility

About

The goals of this protocol are to determine the effect of oxaliplatin, cytosine arabinoside, and dexamethasone with Rituxan (ROAD) as treatment for patients with relapsed CD20+ B-cell non-Hodgkins lymphoma (NHL).

Full description

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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)

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Treatment (ROAD)

Experimental group

Description:

The treatment regimen included oxaliplatin with rituximab, cytarabine, and dexamethasone (ROAD); specifically, rituximab 375 mg/m^2 IV on days 1, 8,15, and 22 (cycle 1 only); dexamethasone 40 mg PO/IV days 2-5; oxaliplatin 130 mg/m^2 IV over 2 hours on day 2; cytarabine 2000 mg/m^2 IV in 250 mL of D5W over three hours x two doses on days 2-3. The second dose of cytarabine was to be given no sooner than 12 hours after the first dose and no later than 24 hours after the conclusion of the first dose. This permitted outpatient administration if desired. Patients were provided pegfilgrastim 6 mg SC on day 4. A cycle was 21 days.

Treatment:

Drug: Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD)