B-Cell Chronic Lymphocytic LeukemiaPhase 3NCT00254163
Fludarabine, Cyclophosphamide, and Rituximab Versus Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-Cell Chronic Lymphocytic Leukemia Patients
A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with B-Cell Chronic Lymphocytic Leukemia, run by US Oncology Research at 11 sites in United States.
Trial summary
The purpose of this research study is to find out what effects (good and bad) the combination of Nipent+Cytoxan+Rituxan has on CLL cancer compared to Fludara+Cytoxan+Rituxan. While all of these drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers, these combinations are… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Chronic Lymphocytic Leukemia
- What is being tested?
- Fludarabine, Cyclophosphamide and Rituximab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 11 sitesUnited States
- Study dates
- Dec 2003to Sep 2011
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for inclusion in this study if they meet all of the following criteria:
- Progressive, histologically proven B-cell CLL.
- Stage II, III, or IV B-cell CLL, as defined by Appendix III.
- Note: The pathology or flow cytometry (of peripheral blood or a bone marrow) report, done by the local laboratory which documents these findings, must be included in the source documents. The SI must review the above pathology report or flow cytometry report results (including bone marrow aspirate analysis and CD5 and CD20 results) by fax, prior to registration, to confirm each patient's eligibility. Results should be consistent with typical B-cell CLL. If Dr. Reynolds is not available to review these documents, they must be reviewed by Dr. Nicholas J. Di Bella.
- Patient must be CD20 +
- Patient must be CD5+ (CD5 >70%)
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- No more than 1 prior course (regimen) of chemotherapy, which can include Fludara or Rituxan
- No prior radiation therapy, except for the treatment of skin cancer or a nonmalignant condition.
- If patient has lymph node involvement, a CT scan confirming measurable tumor size (lymph node must be >1 cm in its longest transverse diameter).
- SI has been notified IF patient is on replacement steroids at time of registration.
- Age greater than 18 years.
- ECOG performance status of 0-2 (Appendix I).
- Normal renal function (creatinine <1.5 mg/dL and BUN <25 mg/dL).
- Absolute neutrophil count (ANC) greater than 1,000 cells/µL, platelet count greater than 50,000 cells/µL, and hemoglobin greater than 9 g/dL.
- Bilirubin less than 2.0 mg/dL, and AST and ALT less than 5 times the upper limit of normal.
- Negative serum pregnancy test within 7 days prior to registration (female patients of childbearing potential).
- Agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter.
- A signed Patient Informed Consent Form has been obtained.
- A signed Patient Authorization Form has been obtained.
Who cannot join
- Patients will be excluded from this study if they meet any of the following criteria:
- Any disease other than histologically confirmed progressive, Stage II, III, or IV CLL.
- Well differentiated lymphocytic lymphoma in nodes without lymphocytosis.
- More than 1 prior course (regimen) of chemotherapy.
- Any radiation for the treatment of CLL.
- Any prior Nipent.
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- Known to be CD20 negative (CD20 <20%).
- Pregnant or lactating, or has a positive pregnancy test.
- Has a history of other malignancy (other than in situ cervical cancer, carcinoma intraepithelial neoplasia, or non-melanoma skin cancer) within the last 5 years, which could affect the administration of these study drugs or assessment of current CLL.
- Known to be HIV positive.
- Uncontrolled thyroid disease or uncontrolled abnormal thyroid function.
- Note: Patients with thyroid disease that is controlled with medication may participate.
- A history of recent, unstable organic heart disease or stable organic heart disease with LVEF <50%.
- A known hypersensitivity to Fludara, Nipent, Rituxan, or Cytoxan, or any component of these drugs.
- Autoimmune hemolytic anemia.
- Unable to comply with requirements of study.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
New York Oncology Hematology, PC
Albany, New York, 12208
Northwestern Carolina Oncology Hemato
Hickory, North Carolina, 28602
Medical Oncology Associates
Kingston, Pennsylvania, 18704
South Texas Cancer Center-McAllen
McAllen, Texas, 78503
Cancer Centers of Florida, P.A.
Ocoee, Florida, 34761
St Joseph Oncology, Inc
Saint Joseph, Missouri, 64507
Cancer Care Northwest-South
Spokane, Washington, 99202
Texas Oncology Cancer Center-Sugar Land
Sugar Land, Texas, 77479
Hope Center
Terre Haute, Indiana, 47802
Alliance Hematology Oncology PA
Westminster, Maryland, 21157
Yakima Valley Mem Hosp/North Star Lodge
Yakima, Washington, 98902
About this study
Official title: A Prospective, Randomized, Open Label, Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab vs. Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-cell Chronic Lymphocytic Leukemia
The purpose of this research study is to find out what effects (good and bad) the combination of Nipent+Cytoxan+Rituxan has on CLL cancer compared to Fludara+Cytoxan+Rituxan. While all of these drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers, these combinations are experimental for the treatment of CLL.
- Conditions
- B-Cell Chronic Lymphocytic Leukemia
- Being tested
- Fludarabine, Cyclophosphamide, Rituximab, Pentostatin
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
CyclophosphamideDrug
RituximabDrug
PentostatinDrug
Also called Nipent
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine, Cyclophosphamide, and Rituximab | Active comparator | Fludarabine, Cyclophosphamide, and Rituximab (dosage based on day in cycle) Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab |
| Pentostatin, Cyclophosphamide, and Rituximab | Experimental | Pentostatin, Cyclophosphamide, and Rituximab (dosage depends on day in cycle) Receives: Drug: Cyclophosphamide; Drug: Rituximab; Drug: Pentostatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infection Rate
infection=febrile events requiring treatment
Measured: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Secondary outcomes (8)
Infective Event Rate
infective events=temperature >101 without symptoms or temp <101 with symptoms
Measured: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Percentage of Patients Hospitalized
Percentage of patients who were hospitalized due to any reasons during the study period.
Measured: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Hematologic Recovery
defined as Hb >11g/dL and a platelet count >100 × 10^3/mm^3
Measured: 2 months post-treatment
Mean Absolute Neutrophil Count (ANC) at Post-treatment
mean Absolute Neutrophil Count (ANC) measured 2 months (8-10 weeks) following the last dose of study treatment
Measured: 2 months post-treatment
Complete Remission (CR)
Definitions of response is evaluated using guidelines proposed by the National Cancer Institute-Sponsored Working Group for Chronic Lymphocytic Leukemia.
Complete remission (CR) requires all of the following for a period of at least 2 months:
- Absence of lymphadenopathy by physical examination and appropriate radiographic techniques. Lymph nodes must be <1 cm.
- No evidence of hepatomegaly or splenomegaly.
- Absence of constitutional symptoms.
- Normal CBC as exhibited by:
- Polymorphonuclear leukocytes ≥ 1,500/mm^3
- Platelets > 100,000/mm^3
- Hemoglobin > 11.0 g/dL (untransfused)
- Bone marrow aspirate and biopsy should be performed 2 months after clinical and laboratory results demonstrate that all of the requirements listed in 1-4 have been met to demonstrate that a CR has been achieved. The marrow sample must be at least normocellular for age, with less than 30% of the nucleated cells being lymphocytes.
Lymphoid nodules should be absent.
Measured: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Objective Remission Rate (ORR)
Complete remission (CR) see Outcome Measure 6. Partial remission (PR) must exhibit criteria 1 and 2 as well as one or more of the remaining features for at least 2 months.
- ≥50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value.
- ≥50% reduction in lymphadenopathy.
- ≥50% reduction in the size of the liver and/or spleen.
- Polymorphonuclear leukocytes ≥ 1,500/mm^3 or 50% improvement over baseline.
- Platelets >100,000/mm^3 or 50% improvement over baseline.
- Hemoglobin >11.0 g/dL or 50% improvement over baseline without transfusions. Nodular partial remission (nPR) is defined as a CR with persistent bone marrow nodules; Objective Remission (OR) = CR + PR + nPR.
Measured: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Progression-free Survival (PFS) Rate at 1-year
PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date
Measured: 12 months after registered.
Progression-free Survival (PFS) Rate at 2-year
PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.
Measured: 24 months after registered.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2005 (estimated)
- Study startDec 2003
- Primary completionSep 2011
- Study completionSep 2011
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 B-Cell Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Oncology Research
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Astex Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Craig Reynolds, MD, Principal investigator, US Oncology Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00254163
- Sponsor's protocol ID
- 03017
- Other IDs
- NIP-03-007
- Status last verified
- Sep 2016
- First submitted
- 9 Nov 2005
- Last updated
- 3 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Randomized, Open Label, Phase III Trial of Fludarabine, Cyclophosphamide, and Rituximab vs. Pentostatin, Cyclophosphamide, and Rituximab in Previously Untreated or Treated B-cell Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00254163
- Acronym / sponsor ID
- 03017
- Conditions
- B-Cell Chronic Lymphocytic Leukemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- US Oncology ResearchIndustry (pharma, biotech, devices)
- Collaborators
- Astex Pharmaceuticals, Inc.
- Study start
- Dec 2003
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 15 Nov 2005 (estimated)
- Results
- Posted 3 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to find out what effects (good and bad) the combination of Nipent+Cytoxan+Rituxan has on CLL cancer compared to Fludara+Cytoxan+Rituxan. While all of these drugs are approved by the Food and Drug Administration (FDA) for the treatment of other cancers, these combinations are experimental for the treatment of CLL.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fludarabine, Cyclophosphamide, and Rituximab | Active comparator | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: RituximabFludarabine, Cyclophosphamide, and Rituximab (dosage based on day in cycle) |
| Pentostatin, Cyclophosphamide, and Rituximab | Experimental | Drug: Cyclophosphamide, Drug: Rituximab, Drug: PentostatinPentostatin, Cyclophosphamide, and Rituximab (dosage depends on day in cycle) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients will be eligible for inclusion in this study if they meet all of the following criteria:
- Progressive, histologically proven B-cell CLL.
- Stage II, III, or IV B-cell CLL, as defined by Appendix III.
- Note: The pathology or flow cytometry (of peripheral blood or a bone marrow) report, done by the local laboratory which documents these findings, must be included in the source documents. The SI must review the above pathology report or flow cytometry report results (including bone marrow aspirate analysis and CD5 and CD20 results) by fax, prior to registration, to confirm each patient's eligibility. Results should be consistent with typical B-cell CLL. If Dr. Reynolds is not available to review these documents, they must be reviewed by Dr. Nicholas J. Di Bella.
- Patient must be CD20 +
Key exclusion criteria (16 listed)
- Any disease other than histologically confirmed progressive, Stage II, III, or IV CLL.
- Well differentiated lymphocytic lymphoma in nodes without lymphocytosis.
- More than 1 prior course (regimen) of chemotherapy.
- Any radiation for the treatment of CLL.
- Any prior Nipent.
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 |
|---|---|---|
| Fludarabine | Drug | Fludarabine, Cyclophosphamide, and Rituximab |
| Cyclophosphamide | Drug | Fludarabine, Cyclophosphamide, and Rituximab, Pentostatin, Cyclophosphamide, and Rituximab |
| Rituximab | Drug | Fludarabine, Cyclophosphamide, and Rituximab, Pentostatin, Cyclophosphamide, and Rituximab |
| PentostatinAlso: Nipent | Drug | Pentostatin, Cyclophosphamide, and Rituximab |
Primary outcome
Infection Rate
Time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
infection=febrile events requiring treatment
8 secondary outcomes
Infective Event Rate
Time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Percentage of Patients Hospitalized
Time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Hematologic Recovery
Time frame: 2 months post-treatment
Mean Absolute Neutrophil Count (ANC) at Post-treatment
Time frame: 2 months post-treatment
Complete Remission (CR)
Time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Objective Remission Rate (ORR)
Time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity
Progression-free Survival (PFS) Rate at 1-year
Time frame: 12 months after registered.
Progression-free Survival (PFS) Rate at 2-year
Time frame: 24 months after registered.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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HPC Offered for PRESERVE Expansion
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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 Reynolds, MD principal investigator
US Oncology Research
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fludarabine, Cyclophosphamide and Rituximab in people with B-Cell Chronic Lymphocytic Leukemia, run by US Oncology Research at 11 sites 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?
The sponsor lists 19 inclusion and 16 exclusion criteria. 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: finished, as of the sponsor's last update on 3 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 Nov 2016). 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?
Infection Rate (time frame: 6 cycles of 28-day for FCR and 8 cycles of 21-day for PCR, or until PD, CR, or intolerable toxicity). 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 3 Nov 2016.