LymphomaPhase 1/2NCT00691652
Clofarabine and Rituximab in Treating Patients With Relapsed Non-Hodgkin Lymphoma
A Phase 1/2 study testing rituximab, clofarabine and DNA methylation analysis in people with Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- rituximab, clofarabine and DNA methylation analysis
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Apr 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed B-cell lymphoma
- Relapsed disease
- CD20-positive disease
- Must have had bone marrow aspiration and biopsy (uni- or bilateral) within the past 42 days and chest CT and CT of the abdomen and pelvis within the past 28 days
- Documented bidimensionally measurable disease within the past 28 days
- Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
PATIENT CHARACTERISTICS:
- Eastern Cooperative Oncology Group(ECOG) performance status 0-2
- Leukocyte count ≥ 3,000/μL
- Absolute neutrophil count ≥ 1,500/μL
- Platelet count ≥ 75,000/μL
- Total bilirubin ≤ 2 times upper limit of normal (ULN)
- AST and ALT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 30 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for at least 6 months after completion of study therapy
- No known AIDS or HIV-associated complex
- No active hepatitis B infection
- No other severe concurrent disease, history of serious organ dysfunction, or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
- No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment
- No history of intolerance or allergic reactions to clofarabine or rituximab
- No significant concurrent disease, illness, or psychiatric disorder that would compromise the patient's safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
- No concurrent active GI disease that may impair absorption of oral clofarabine
PRIOR CONCURRENT THERAPY:
- Recovered from all previous therapies
- No prior gastrointestinal (GI) surgery that may impair absorption of oral clofarabine
- More than 2 weeks since prior and no concurrent anticancer therapy, except for hydroxyurea
- More than 4 weeks since prior radioimmunotherapy
- More than 1 month since prior investigational agents
- No concurrent cytotoxic therapy or investigational therapy
- No other concurrent investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy
- No concurrent alternative medications (e.g., herbal or botanical for anticancer purposes)
- No other concurrent chemotherapy or immunotherapy
- No concurrent radiotherapy
- No concurrent colony stimulating factors (phase I portion of the study)
Trial locations and contacts
1 site in 1 country.
United States1 site
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, 97239-3098
About this study
Official title: Phase I/II Study of Oral Clofarabine + Rituximab in Relapsed B Cell NHL
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.
Read the detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of clofarabine in adult patients with relapsed CD20-positive B-cell non-Hodgkin lymphoma (NHL).
- To estimate objective response rates of clofarabine in combination with rituximab in these patients.
Secondary
- To determine the 1-year progression-free survival of this regimen using the mean tolerated dose in these patients.
- To determine the safety and efficacy of this regimen in these patients.
- To determine if clofarabine acts as an inhibitor of DNA methylation similar to cladribine by performing scientific correlates.
- To determine whether response to clofarabine alone or in combination with rituximab correlates with changes in global serum DNA methylation index.
- To identify the gene activated by clofarabine therapy by using genomic DNA and RNA array technology.
OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study.
Patients receive oral clofarabine once daily on days 1-14 of all courses and rituximab IV on days 1, 8, 15, and 22 of course one and then on day 1 of courses 2-8. Courses repeat every 4 weeks. After 2 courses of therapy, patients who are eligible for stem cell transplantation may either undergo transplantation or continue receiving study drugs until disease progression or unacceptable toxicity for up to a total of 8 courses of treatment.
Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed to identify global DNA methylation differences and correlate changes in methylation index (MI) with patient outcome after treatment with clofarabine with or without rituximab via high performance liquid chromatography (HPLC); to determine differences in gene expression via microarray analysis and micro-RNA (miRNA) expression via quantitative polymerase chain reaction (PCR) in patients with high compared to low global DNA methylation index and miRNA expression for CD5+ B-lymphocytes obtained from pediatric tonsils and from B-lymphocytes of 5 healthy controls; and to determine gene expression and miRNA profiles in patients before and after treatment with clofarabine with or without rituximab via genomic DNA arrays.
After completion of study treatment, patients are followed once a year for 2 years.
- Conditions
- Lymphoma
- Being tested
- rituximab, clofarabine, DNA methylation analysis, gene expression analysis, microarray analysis
- Keywords
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, cutaneous B-cell non-Hodgkin lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
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.
clofarabineDrug
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 analysisGenetic
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 analysisGenetic
Total RNA will be processed for determination of gene expression by microarray
microarray analysisGenetic
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 reactionGenetic
high performance liquid chromatographyOther
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 analysisOther
Also called High Performance Liquid Chromatography (HPLC)
50 µl of the clear supernatant is injected into the reverse-phase high performance liquid chromatography (HPLC).
| Study group | Role | What they receive |
|---|---|---|
| Oral Clofarabine + Rituximab in Relapsed B Cell NHL | Experimental | 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 Receives: Biological: rituximab; Drug: clofarabine; Genetic: DNA methylation analysis; Genetic: gene expression analysis; Genetic: microarray analysis; Genetic: polymerase chain reaction; Other: high performance liquid chromatography; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose (MTD) of Oral Clofarabine in Adult Patients With Relapsed CD20+ Non-Hodgkin Lymphoma(NHL)
Initially, 3 patients will be enrolled into a dose level during the dose-escalation portion:
- If no patient experiences dose-limiting toxicities during the first 4 weeks, then 3 patients will be enrolled into the next dose level.
- If one of the three patients develops dose-limiting toxicities, then 3 additional patients will be enrolled in that cohort. If none of the additional 3 patients experiences dose-limiting toxicities, then further dose-escalation occurs.
- If one additional patient experiences dose-limiting toxicities, then the maximum tolerated dose is exceeded.
Measured: 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
Estimate Objective Response Rates of Oral Clofarabine in Combination With Rituximab in Relapsed CD20+NHL
Measured: Oral Clofarabine x 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 AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle
Secondary outcomes (5)
Determine One-year Progression Free Survival Using the MTD of Clofarabine With Rituximab in Relapsed CD20+NHL
Measured: One year after study drug(s) have been given. Duration of study up to 1 year.
Determine the Safety and Efficacy of Clofarabine in Combination With Rituximab
Measured: Duration of the study, up to 1 year.
Whether Clofarabine Acts as an Inhibitor of DNA Methylation Similar to Cladribine by Performing Scientific Correlates
Measured: Duration of the study, up to 1 year.
Whether Response to Clofarabine Alone or in Combination With Rituximab Correlates With Changes in Global Serum DNA Methylation Index
Measured: Duration of the study, up to 1 year.
Identity of the Gene Activated by Clofarabine Therapy by Using Genomic DNA and RNA Array Technology
Measured: Twice monthly at standard of care visits for 3 months post last cycle of chemotherapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2008 (estimated)
- Study startMay 2008
- Primary completionJan 2009
- Study completionApr 2009
Why it stopped: Funding ended when only one subject enrolled and subject withdrew early.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Craig Okada, MD, PhD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00691652
- Sponsor's protocol ID
- CDR0000597410
- Other IDs
- P30CA069533, OHSU-HEM-07156-L, IRB#4101, GENZYME-OHSU-HEM-07156-L
- Status last verified
- Nov 2019
- First submitted
- 4 Jun 2008
- Last updated
- 27 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Oral Clofarabine + Rituximab in Relapsed B Cell NHL
- ClinicalTrials.gov ID
- NCT00691652
- Acronym / sponsor ID
- CDR0000597410
- Conditions
- Lymphoma
- Keywords
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade III lymphomatoid granulomatosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding ended when only one subject enrolled and subject withdrew early.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- OHSU Knight Cancer InstituteUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- May 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Apr 2009 (actual)
- First posted
- 5 Jun 2008 (estimated)
- Results
- Posted 16 Sep 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of clofarabine in adult patients with relapsed CD20-positive B-cell non-Hodgkin lymphoma (NHL).
- To estimate objective response rates of clofarabine in combination with rituximab in these patients.
Secondary
- To determine the 1-year progression-free survival of this regimen using the mean tolerated dose in these patients.
- To determine the safety and efficacy of this regimen in these patients.
- To determine if clofarabine acts as an inhibitor of DNA methylation similar to cladribine by performing scientific correlates.
- To determine whether response to clofarabine alone or in combination with rituximab correlates with changes in global serum DNA methylation index.
- To identify the gene activated by clofarabine therapy by using genomic DNA and RNA array technology.
OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study.
Patients receive oral clofarabine once daily on days 1-14 of all courses and rituximab IV on days 1, 8, 15, and 22 of course one and then on day 1 of courses 2-8. Courses repeat every 4 weeks. After 2 courses of therapy, patients who are eligible for stem cell transplantation may either undergo transplantation or continue receiving study drugs until disease progression or unacceptable toxicity for up to a total of 8 courses of treatment.
Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed to identify global DNA methylation differences and correlate changes in methylation index (MI) with patient outcome after treatment with clofarabine with or without rituximab via high performance liquid chromatography (HPLC); to determine differences in gene expression via microarray analysis and micro-RNA (miRNA) expression via quantitative polymerase chain reaction (PCR) in patients with high compared to low global DNA methylation index and miRNA expression for CD5+ B-lymphocytes obtained from pediatric tonsils and from B-lymphocytes of 5 healthy controls; and to determine gene expression and miRNA profiles in patients before and after treatment with clofarabine with or without rituximab via genomic DNA arrays.
After completion of study treatment, patients are followed once a year for 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oral Clofarabine + Rituximab in Relapsed B Cell NHL | Experimental | Biological: rituximab, Drug: clofarabine, Genetic: DNA methylation analysis, Genetic: gene expression analysis, Genetic: microarray analysis, Genetic: polymerase chain reaction, Other: high performance liquid chromatography, Other: laboratory biomarker analysisPhase 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 |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rituximabAdministered 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. | Biological | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| clofarabinePhase 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. | Drug | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| DNA methylation analysisWe 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 | Genetic | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| gene expression analysisTotal RNA will be processed for determination of gene expression by microarray | Genetic | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| microarray analysiswe 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. | Genetic | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| polymerase chain reaction | Genetic | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| high performance liquid chromatographyFifteen 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). | Other | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
| laboratory biomarker analysisAlso: High Performance Liquid Chromatography (HPLC)50 µl of the clear supernatant is injected into the reverse-phase high performance liquid chromatography (HPLC). | Other | Oral Clofarabine + Rituximab in Relapsed B Cell NHL |
Primary outcome
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
Initially, 3 patients will be enrolled into a dose level during the dose-escalation portion: * If no patient experiences dose-limiting toxicities during the first 4 weeks, then 3 patients will be enrolled into the next dose level. * If one of the three patients develops dose-limiting toxicities, then 3 additional patients will be enrolled in that cohort. If none of the additional 3 patients experiences dose-limiting toxicities, then further dose-escalation occurs. * If one additional patient experiences dose-limiting toxicities, then the maximum tolerated dose is exceeded.
Estimate Objective Response Rates of Oral Clofarabine in Combination With Rituximab in Relapsed CD20+NHL
Time frame: Oral Clofarabine x 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 AND Rituximab weekly for 4 weeks than monthly for up to 8 cycles on day 1 of cycle
5 secondary outcomes
Determine One-year Progression Free Survival Using the MTD of Clofarabine With Rituximab in Relapsed CD20+NHL
Time frame: One year after study drug(s) have been given. Duration of study up to 1 year.
Determine the Safety and Efficacy of Clofarabine in Combination With Rituximab
Time frame: Duration of the study, up to 1 year.
Whether Clofarabine Acts as an Inhibitor of DNA Methylation Similar to Cladribine by Performing Scientific Correlates
Time frame: Duration of the study, up to 1 year.
Whether Response to Clofarabine Alone or in Combination With Rituximab Correlates With Changes in Global Serum DNA Methylation Index
Time frame: Duration of the study, up to 1 year.
Identity of the Gene Activated by Clofarabine Therapy by Using Genomic DNA and RNA Array Technology
Time frame: Twice monthly at standard of care visits for 3 months post last cycle of chemotherapy.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Okada, MD, PhD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rituximab, clofarabine and DNA methylation analysis in people with Lymphoma, run by OHSU Knight Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2019.