Lymphoma
Conditions
Keywords
C04.557.386
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).
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.
Interventions
DRUGOxaliplatin, 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
Sponsors
Mayo Clinic
Academic and Community Cancer Research United
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate After Two Cycles of ROAD | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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. |
| Progression-free Survival | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 5 |
Baseline characteristics
| Characteristic | Treatment (ROAD) |
|---|---|
| Age, Continuous | 69 years |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 26 / 45 |
| other Total, other adverse events | 43 / 45 |
| serious Total, serious adverse events | 3 / 45 |
Outcome results
Primary
Overall Response Rate After Two Cycles of ROAD
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.
Time frame: Up to 42 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (ROAD) | Overall Response Rate After Two Cycles of ROAD | 58 percentage of patients |
Secondary
Overall Survival
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.
Time frame: Up to 10 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (ROAD) | Overall Survival | 26 months |
Secondary
Progression-free Survival
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.
Time frame: Up to 10 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (ROAD) | Progression-free Survival | 11 months |