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

• Sponsor: Academic and Community Cancer Research United (Other)
• Overall Status: Completed
• CT.gov ID: NCT00166439
• Collaborator: Mayo Clinic (Other)
• Enrollment: 50
• Location: 1
• Arm: 1
• Actual Duration (Months): 126
• Patients Per Site Per Month: 0.4

Study Details

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
• 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: Mar 1, 2005
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 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 [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 [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT00166439
• Other Study ID Numbers: MC0485; MC0485; 2328-04
• First Posted: Sep 14, 2005
• Last Update Posted: Jan 14, 2020
• Last Verified: Oct 1, 2015

• Keywords provided by Academic and Community Cancer Research United: C04.557.386
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Cytarabine; Dexamethasone; Oxaliplatin; Rituximab

Study Results

Participant Flow

Arm/Group Title	Treatment (ROAD)
Arm/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.
Period Title: Overall Study
STARTED	50
COMPLETED	45
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Treatment (ROAD)
Arm/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.
Overall Participants	45
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	21 46.7%
Male	24 53.3%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate After Two Cycles of ROAD
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (ROAD)
Arm/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.
Measure Participants	45
Number (95% Confidence Interval) [percentage of patients]	58

2. Secondary Outcome

Title	Overall Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (ROAD)
Arm/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.
Measure Participants	45
Median (95% Confidence Interval) [months]	26

3. Secondary Outcome

Title	Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (ROAD)
Arm/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.
Measure Participants	45
Median (95% Confidence Interval) [months]	11

Adverse Events

Arm/Group Title	Treatment (ROAD)
Arm/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.
All Cause Mortality
	Treatment (ROAD)
	Affected / at Risk (%)	# Events
Total	26/45 (57.8%)
Serious Adverse Events
	Treatment (ROAD)
	Affected / at Risk (%)	# Events
Total	3/45 (6.7%)
Gastrointestinal disorders
Small intestinal obstruction	1/45 (2.2%)	1
Investigations
Platelet count decreased	1/45 (2.2%)	1
Renal and urinary disorders
Ureteric obstruction	1/45 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Treatment (ROAD)
	Affected / at Risk (%)	# Events
Total	43/45 (95.6%)
Blood and lymphatic system disorders
Febrile neutropenia	8/45 (17.8%)	8
Hemoglobin decreased	19/45 (42.2%)	36
Cardiac disorders
Atrial fibrillation	1/45 (2.2%)	1
Atrial tachycardia	1/45 (2.2%)	1
Left ventricular dysfunction	1/45 (2.2%)	1
Gastrointestinal disorders
Abdominal pain	2/45 (4.4%)	2
Anal pain	1/45 (2.2%)	1
Constipation	1/45 (2.2%)	1
Diarrhea	6/45 (13.3%)	9
Dysphagia	1/45 (2.2%)	1
Mucositis oral (funct/sympt)	4/45 (8.9%)	4
Nausea	33/45 (73.3%)	51
Rectal hemorrhage	1/45 (2.2%)	1
Upper gastrointestinal hemorrhage	1/45 (2.2%)	1
Vomiting	22/45 (48.9%)	28
General disorders
Edema limbs	2/45 (4.4%)	2
Fatigue	20/45 (44.4%)	30
Fever	4/45 (8.9%)	4
Immune system disorders
Hypersensitivity	1/45 (2.2%)	1
Infections and infestations
Anal infection(gr 3/4 ANC)	1/45 (2.2%)	1
Infection(gr 0/1/2 ANC)	1/45 (2.2%)	1
Lip infection(unknown ANC)	1/45 (2.2%)	1
Pneumonia(gr 0/1/2 ANC)	3/45 (6.7%)	3
Pneumonia(gr 3/4 ANC)	3/45 (6.7%)	3
Pneumonia(unknown ANC)	1/45 (2.2%)	1
Sepsis(gr 0/1/2 ANC)	2/45 (4.4%)	2
Skin infection(gr 3/4 ANC)	1/45 (2.2%)	1
Upper respiratory infectn(gr 0/1/2 ANC)	1/45 (2.2%)	1
Upr aerodigstve trct infctn(gr0/1/2 ANC)	1/45 (2.2%)	1
Urinary tract infection(gr 0/1/2 ANC)	2/45 (4.4%)	2
Investigations
Alkaline phosphatase increased	2/45 (4.4%)	2
Aspartate aminotransferase increased	2/45 (4.4%)	2
Creatinine increased	6/45 (13.3%)	6
Leukocyte count decreased	18/45 (40%)	31
Lymphocyte count decreased	5/45 (11.1%)	10
Neutrophil count decreased	20/45 (44.4%)	36
Platelet count decreased	31/45 (68.9%)	65
Metabolism and nutrition disorders
Anorexia	9/45 (20%)	11
Blood glucose increased	9/45 (20%)	18
Dehydration	6/45 (13.3%)	8
Serum albumin decreased	3/45 (6.7%)	4
Serum calcium decreased	2/45 (4.4%)	3
Serum magnesium decreased	16/45 (35.6%)	21
Serum phosphate decreased	2/45 (4.4%)	2
Serum potassium decreased	18/45 (40%)	23
Serum potassium increased	1/45 (2.2%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/45 (4.4%)	2
Bone pain	1/45 (2.2%)	1
Nervous system disorders
Ataxia	1/45 (2.2%)	1
Dizziness	1/45 (2.2%)	1
Dysgeusia	1/45 (2.2%)	1
Peripheral motor neuropathy	1/45 (2.2%)	1
Peripheral sensory neuropathy	25/45 (55.6%)	47
Recurrent laryngeal nerve palsy	1/45 (2.2%)	1
Syncope	1/45 (2.2%)	1
Syncope vasovagal	1/45 (2.2%)	1
Psychiatric disorders
Confusion	1/45 (2.2%)	1
Insomnia	2/45 (4.4%)	2
Renal and urinary disorders
Proteinuria	1/45 (2.2%)	1
Renal failure	1/45 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/45 (2.2%)	1
Dyspnea	4/45 (8.9%)	5
Hiccups	3/45 (6.7%)	3
Hypoxia	1/45 (2.2%)	1
Pharyngeal mucositis (clin exam)	1/45 (2.2%)	1
Voice alteration	1/45 (2.2%)	1
Skin and subcutaneous tissue disorders
Alopecia	3/45 (6.7%)	6
Dry skin	1/45 (2.2%)	1
Rash desquamating	1/45 (2.2%)	1
Sweating	2/45 (4.4%)	2
Vascular disorders
Hypotension	4/45 (8.9%)	4
Thrombosis	1/45 (2.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.