LeukemiaPhase 2NCT00003659
Fludarabine, Cyclophosphamide, and Rituximab in Treating Patients Who Have Chronic Lymphocytic Leukemia
A Phase 2 study testing filgrastim, rituximab and cyclophosphamide in people with Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Leukemia
- What is being tested?
- filgrastim, rituximab and cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 1998to May 2009
- Phase
- Phase 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have either intermediate or high-risk chronic lymphocytic leukemia as defined by the three-stage Rai system (see section 2.2 page 2). Patients with Rai intermediate risk disease should meet the criteria for active disease as outlined by the NCI Working Group guidelines (including weight loss, fatigue, fevers, evidence of progressive marrow failure, splenomegaly, progressive lymphadenopathy, or progressive lymphocytosis with a rapid doubling time).
- Patients must be previously untreated (with cytoreductive agents) for their CLL.
- The patient must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes/μl, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells. These lymphocytes must have an appropriate immunophenotype for CLL including expression of CD5 and CD20.
- Karnofsky performance status equal to or greater than 60% (see Appendix B).
- Eligible patients should have a reasonable life-expectancy greater than four weeks.
- Age ≥ 18 years and ≤ 75 years.
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- Total bilirubin ≤ 2.0 mg per deciliter. Total creatinine ≤ 2.0 mg/ dl.
- Platelet count ≥ 50,000/ ul.
- Signed informed consent, which indicates the investigational nature of this, is required.
- No patient may be entered onto the study without consultation with the principal investigator.
Who cannot join
- Patients with Rai intermediate risk disease who meet the criteria of Montserrat "smouldering leukemia" will not be eligible for treatment on this protocol.
- Patients with significant autoimmune hemolytic anemia or autoimmune thrombocytopenia shall not be eligible for treatment on this protocol as there is some evidence that fludarabine can worsen these conditions.
- Patients with active infections requiring systemic antibiotics.
- Prior cytotoxic treatment of their CLL.
- Pregnant or lactating women. Women and men of childbearing age should use effective contraception.
- Patients with a serious cardiac condition.
- Concomitant chemotherapy or radiotherapy while on protocol.
- Concomitant prednisone therapy will not be permitted as the combination of fludarabine and prednisone is known to increase the risk of opportunistic infections. Patients may receive intravenous immunoglobulin (IVIG) and other supportive care measures as clinically appropriate while on protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: A Phase II Study of Fludarabine Induction With Sequential High Dose Cyclophosphamide and Rituximab as Consolidation Therapy for Previously Untreated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.
PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose cyclophosphamide and rituximab in treating patients who have previously untreated chronic lymphocytic leukemia.
Read the detailed description
OBJECTIVES:
- Determine the response rate in patients with chronic lymphocytic leukemia treated with sequential fludarabine, high dose cyclophosphamide, and rituximab.
- Survival up to 5 years
- Utilize flow cytometry and polymerase chain reaction as sensitive measures of minimal residual disease in these patients.
OUTLINE: This is an open label study.
Patients receive fludarabine IV once daily for 5 days. Treatment is repeated every 4 weeks for 3 or 6 courses.
Three weeks later, cyclophosphamide is administered intravenously every 2-3 weeks for 3 courses. Filgrastim (G-CSF) is administered on days 2-10. Beginning 4 weeks after the last dose of cyclophosphamide, patients receive rituximab by intravenous infusion once weekly for 4 weeks.
Patient are followed every 3 months until death.
PROJECTED ACCRUAL: This study will accrue 30 patients within 3 years.
- Conditions
- Leukemia
- Being tested
- filgrastim, rituximab, cyclophosphamide, fludarabine phosphate
- Keywords
- stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Medical subject headings
- Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Filgrastim (300 μg for patients ≤ 70 kg or 480 μg for patients > 70 kg) will be administered beginning two days after each cyclophosphamide dose and given for a total of eight subcutaneous daily doses.
rituximabBiological
Approximately four weeks after the completion of the last cyclophosphamide dose, patients will receive rituximab 375mg/m2 as an intravenous infusion once weekly for four doses.
cyclophosphamideDrug
Cyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses.
Fludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| intermediate or high risk chronic lymphocytic leukemia | Experimental | This is a single-arm open-label pilot study designed to assess the antileukemic activity of a regimen containing sequential administration of fludarabine, high-dose cyclophosphamide, and rituximab. Receives: Biological: filgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: fludarabine phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Response was determined as indicated in the protocol. The categories are: complete response, nodular partial response, partial response and failure. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. The laboratory and radiographic studies which were abnormal pre-study, will be repeated to document the degree of maximal response.
Measured: 3 years
Secondary outcomes (2)
Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease
The flow cytometric response and the molecular polymerase chain reaction (PCR) response was captured as indicated in the protocol. Immunophenotypic analysis of bone marrow and/ or peripheral blood demonstrate a normal k:λ ratio and a normal number of CD5/CD19 (or CD5/CD20) dual staining cells (<5% of the lymphocyte gate).
Measured: 3 years
Overall Survival Status
The 5 year survival rate. The survival of patients with this disease is dependent on the stage of disease. Two useful staging systems are: Three-stage Rai System Clinical Feature and the Binet System.
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 1998
- Primary completionMay 2009
- Study completionMay 2009
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mark Adam Weiss, MD, Study chair, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003659
- Sponsor's protocol ID
- 98-080
- Other IDs
- MSKCC-98080, NCI-G98-1483
- Status last verified
- Sep 2017
- First submitted
- 1 Nov 1999
- Last updated
- 24 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Fludarabine Induction With Sequential High Dose Cyclophosphamide and Rituximab as Consolidation Therapy for Previously Untreated Patients With Intermediate and High-Risk Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00003659
- Acronym / sponsor ID
- 98-080
- Conditions
- Leukemia
- Keywords
- stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 1998
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 31 Dec 2012
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 use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.
PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose cyclophosphamide and rituximab in treating patients who have previously untreated chronic lymphocytic leukemia.
Detailed description
OBJECTIVES:
- Determine the response rate in patients with chronic lymphocytic leukemia treated with sequential fludarabine, high dose cyclophosphamide, and rituximab.
- Survival up to 5 years
- Utilize flow cytometry and polymerase chain reaction as sensitive measures of minimal residual disease in these patients.
OUTLINE: This is an open label study.
Patients receive fludarabine IV once daily for 5 days. Treatment is repeated every 4 weeks for 3 or 6 courses.
Three weeks later, cyclophosphamide is administered intravenously every 2-3 weeks for 3 courses. Filgrastim (G-CSF) is administered on days 2-10. Beginning 4 weeks after the last dose of cyclophosphamide, patients receive rituximab by intravenous infusion once weekly for 4 weeks.
Patient are followed every 3 months until death.
PROJECTED ACCRUAL: This study will accrue 30 patients within 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| intermediate or high risk chronic lymphocytic leukemia | Experimental | Biological: filgrastim, Biological: rituximab, Drug: cyclophosphamide, Drug: fludarabine phosphateThis is a single-arm open-label pilot study designed to assess the antileukemic activity of a regimen containing sequential administration of fludarabine, high-dose cyclophosphamide, and rituximab. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have either intermediate or high-risk chronic lymphocytic leukemia as defined by the three-stage Rai system (see section 2.2 page 2). Patients with Rai intermediate risk disease should meet the criteria for active disease as outlined by the NCI Working Group guidelines (including weight loss, fatigue, fevers, evidence of progressive marrow failure, splenomegaly, progressive lymphadenopathy, or progressive lymphocytosis with a rapid doubling time).
- Patients must be previously untreated (with cytoreductive agents) for their CLL.
- The patient must have an absolute lymphocytosis in the blood of at least 5,000 lymphocytes/μl, or bone marrow lymphocytosis greater than or equal to 30% of all nucleated cells. These lymphocytes must have an appropriate immunophenotype for CLL including expression of CD5 and CD20.
- Karnofsky performance status equal to or greater than 60% (see Appendix B).
- Eligible patients should have a reasonable life-expectancy greater than four weeks.
Key exclusion criteria (8 listed)
- Patients with Rai intermediate risk disease who meet the criteria of Montserrat "smouldering leukemia" will not be eligible for treatment on this protocol.
- Patients with significant autoimmune hemolytic anemia or autoimmune thrombocytopenia shall not be eligible for treatment on this protocol as there is some evidence that fludarabine can worsen these conditions.
- Patients with active infections requiring systemic antibiotics.
- Prior cytotoxic treatment of their CLL.
- Pregnant or lactating women. Women and men of childbearing age should use effective contraception.
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 |
|---|---|---|
| filgrastimFilgrastim (300 μg for patients ≤ 70 kg or 480 μg for patients > 70 kg) will be administered beginning two days after each cyclophosphamide dose and given for a total of eight subcutaneous daily doses. | Biological | intermediate or high risk chronic lymphocytic leukemia |
| rituximabApproximately four weeks after the completion of the last cyclophosphamide dose, patients will receive rituximab 375mg/m2 as an intravenous infusion once weekly for four doses. | Biological | intermediate or high risk chronic lymphocytic leukemia |
| cyclophosphamideCyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses. | Drug | intermediate or high risk chronic lymphocytic leukemia |
| fludarabine phosphateFludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks. | Drug | intermediate or high risk chronic lymphocytic leukemia |
Primary outcome
Overall Response Rate
Time frame: 3 years
Response was determined as indicated in the protocol. The categories are: complete response, nodular partial response, partial response and failure. The major criteria for determination of response to therapy in patients with CLL include physical examination and examination of the peripheral blood and bone marrow. The laboratory and radiographic studies which were abnormal pre-study, will be repeated to document the degree of maximal response.
2 secondary outcomes
Utilize Flow Cytometry and Polymerase Chain Reaction as Sensitive Measures of Minimal Residual Disease
Time frame: 3 years
Overall Survival Status
Time frame: up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Mark Adam Weiss, MD study chair
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing filgrastim, rituximab and cyclophosphamide in people with Leukemia, run by Memorial Sloan Kettering Cancer Center 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?
The sponsor lists 10 inclusion and 8 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 24 Oct 2017. 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 phase mean?
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 31 Dec 2012). 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?
Overall Response Rate (time frame: 3 years). 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 24 Oct 2017.