Clofarabine and Rituximab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

Part of paid clinical trials in Portland, Oregon.

Sponsor
OHSU Knight Cancer Institute
Study ID
NCT00691652
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 89 Years
Healthy Volunteers
Not accepted

Interventions

  • rituximab — BIOLOGICAL
    Administered weekly times 4 weeks and then monthly during the study for up to 8 cycles and will be given on day 1 of clofarabine. A peripheral or central intravenous (IV) line will be established. The initial dose rate at the time of the first infusion should be 50/mg/hr for the first hour. If no toxicity is seen, the dose rate may be gradually escalated (50 mg/hr increments at 30 minute intervals) to a maximum of 300 mg/hr. If the first dose of rituximab is well tolerated, the starting flow rate for the administration of subsequent doses will be 100 mg/hr then gradually increased (100 mg/hr increments at 30 minute intervals) not to exceed 400 mg/hr.
  • clofarabine — DRUG
    Phase 1 dosing: Initially, 3 patients will be enrolled into a dose level during the dose escalation portion. Level 1: 2mg fixed dose times 14 days for up to 8 cycles. Level 2: 4mg fixed dose times 14 days for up to 8 cycles. Level 3: 6mg fixed dose times 14 days for up to 8 cycles. Phase II dosing: The phase II dose of oral clofarabine will be determined from the phase 1.
  • DNA methylation analysis — GENETIC
    We will use an HPLC assay developed by Yu et al31 to determine the DNA methylation (DMI) index in peripheral blood and bone marrow of patients entering this trial and after treatment with clofarabine and rituxan
  • gene expression analysis — GENETIC
    Total RNA will be processed for determination of gene expression by microarray
  • microarray analysis — GENETIC
    we will scan the microarray slides with an Axon scanner, and quantify data using the GeneSight software. Local background is subtracted and data points with no signal, high background, or spot asymmetry are eliminated. We will adjust genes with low expression and low signal intensity to a minimal raw value of 5: This avoids unwarranted mathematical distortions due to division by decimals \<\< 1. After calculating the ratio of the Cy5 /Cy3 fluorescence signal intensity for each gene, we normalize the data relative to the mean intensity from all genes.
  • polymerase chain reaction — GENETIC
  • high performance liquid chromatography — OTHER
    Fifteen µg of DNA will be sonicated for 60 seconds on ice into 200 bp-1000 bp fragments. Samples are then denatured at 1000C for 5 minutes and cooled on ice to prevent re-annealing. Sixty units of nuclease S1 (Invitrogen) and 112.5 mu of snake venom phosphodiesterase I (Sigma) in 12 µl of S1 dilution buffer is then added to the samples and incubated at 370C for 18 hours. Samples are reheated to 1000C for 5 minutes, snap cooled again on ice, and another sixty units of nuclease S1 and 112.5 mu of snake venom phosphodiesterase I are added and incubated at 370C for another 4 to 6 hours. The pH of each sample was raised to 8.5 with 0.5 M Tris, pH 10. Two and a half units of alkaline phosphatase (Sigma) are added and incubated for 2 additional hours at 370C. One hundred µl of 0.05M potassium phosphate, pH 7 is added to final samples before 50 µl of the clear supernatant is injected into the reverse-phase high performance liquid chromatography (HPLC).
  • laboratory biomarker analysis — OTHER
    50 µl of the clear supernatant is injected into the reverse-phase high performance liquid chromatography (HPLC).

Study Details

RATIONALE: Drugs used in chemotherapy, such as clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving clofarabine together with rituximab may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with rituximab and to see how well they work in treating patients with relapsed B-cell non-Hodgkin lymphoma.

Key Dates

Start date
May 31, 2008
Status verified
Nov 2019
Primary completion
Jan 31, 2009
Completion
Apr 30, 2009

Study Design

Enrollment
2 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Oral Clofarabine + Rituximab in Relapsed B Cell NHL
    Phase I: Oral Clofarabine x 14 days for up to 8 cycles at assigned dose level below (1 cycle equals 14 days on drug, 14 days off). Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV Dose Level 1: 2 mg Dose Level 2: 4 mg Dose Level 3: 6 mg Phase II: Oral Clofarabine x 14 days for up to 8 cycles (Dose determined from phase I) AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle 375 mg/m2 IV

Primary Outcome Measure

The Maximum Tolerated Dose (MTD) of Oral Clofarabine in Adult Patients With Relapsed CD20+ Non-Hodgkin Lymphoma(NHL) [ Time Frame: 14 days for up to 8 cycles (1 cycle equals 14 days on drug, 14 days off drug) for a total of up to 224 days ]

Locations (1)

FacilityCityStateZIPSite coordinators
Knight Cancer Institute at Oregon Health and Science UniversityPortlandOregon97239-3098-

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By research site
Knight Cancer Institute at Oregon Health and Science University· Portland, OR

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