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

• ClinicalTrials.gov Identifier: NCT00166439
• Recruitment Status: Completed
• First Posted: September 14, 2005
• Results First Posted: January 14, 2020
• Last Update Posted: January 14, 2020
• Sponsor: Academic and Community Cancer Research United
• Collaborator: Mayo Clinic
• Information provided by (Responsible Party): Academic and Community Cancer Research United

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD)	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD) in Patients With Relapsed CD20+ B-Cell Non-Hodgkins Lymphoma
• Actual Study Start Date: March 2005
• Actual Primary Completion Date: September 2015
• Actual Study Completion Date: September 2015

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment (ROAD); 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.

Drug: Oxaliplatin, Cytosine Arabinoside, Dexamethasone With Rituxan (ROAD); rituximab 375 mg/m2 IV Weekly x 4 1 cycle only dexamethasone 40 mg PO/IV Days 2-5 q 21 days 2 cycles oxaliplatin 130 mg/m2 IV Day 2 q 21 days 2 cycles cytosine arabinoside 2000 mg/m2 x 2 doses IV Days 2-3 q 21 days 2 cycles pegfilgrastim 6 mg SQ Day 4 q21 days 2 cycles

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate After Two Cycles of ROAD [ Time Frame: Up to 42 days ]
   The overall response rate is defined as the percentage of patients who achieve a response after two cycles of oxaliplatin with rituximab, cytarabine, and dexamethasone (ROAD). A response was considered a Complete Response (CR) or Partial Response (PR) as defined by the NCI Sponsored International Working Group (IWG). CR: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities PR: ≥ 50% decrease in SPD of the six largest dominant nodes or nodal masses.

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: Up to 10 years ]
   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
2. Progression-free Survival [ Time Frame: Up to 10 years ]
   The progression-free survival time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Progression is defined by the NCI Sponsored IWG as a ≥ 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or nonresponders and/or Appearance of any new lesion during or at the end of therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Academic and Community Cancer Research United

Mayo Clinic

Investigators

• Principal Investigator: Patrick B. Johnston, M.D., Ph.D.; Mayo Clinic

More Information

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT00166439
• Other Study ID Numbers: MC0485; MC0485 ( Other Identifier: Mayo Clinic Cancer Center ); 2328-04 ( Other Identifier: Mayo Clinic IRB )
• First Posted: September 14, 2005
• Results First Posted: January 14, 2020
• Last Update Posted: January 14, 2020
• Last Verified: October 2015

Keywords provided by Academic and Community Cancer Research United:

C04.557.386

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Dexamethasone; Oxaliplatin; Rituximab; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immunologic Factors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents