Chronic Lymphocytic LeukemiaPhase 2NCT00280241
Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
A Phase 2 study testing Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by University of Pittsburgh at 1 site in United States.
Trial summary
This research study will look at the effects (good or bad) of administering cyclophosphamide, fludarabine, and rituximab. Clinical studies with combination therapy have shown higher response rates than using single drugs, and this study will evaluate the side effects and effectiveness of this combination. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia
- What is being tested?
- Fludarabine, Cyclophosphamide and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Jan 2013
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of CD20 + CLL
- Peripheral blood absolute lymphocyte count of > 5,000/mm3 obtained within 2 weeks prior to randomization.
- The lymphocytosis must consist of small to moderate size lymphocytes, with ≤55% (no greater than 55%) prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically.
- Phenotypically characterized CD20 + CLL defined as: 1) the predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-celI markers (CD3, CD2, etc.); 2) B-cell expresses either kappa or lambda light chains; and 3) surface immunoglobulin (slg) with low-cell surface density expression.
- Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL.
- Must require chemotherapy. Indications for chemotherapy are one or more of the following:
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- One or more of the following disease-related symptoms
- Weight loss >10% within the previous 6 months.
- Fevers of greater than 100.0° F for 2 weeks without evidence of infection.
- Night sweats without evidence of infection.
- Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (< 10 g/dl) and/or thrombocytopenia (< 100,000/mm3).
- Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly.
- Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive
- adenopathy.
- Progressive lymphocytosis with an increase of> 50% over 2 month period, or an anticipated doubling time of less than 6 months.
- NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease are not sufficient for protocol therapy.
- Serum creatinine <1.5 mg/dl.
- Bilirubin must be <2 mg/dl, unless secondary to tumor, obtained within 2 weeks prior to randomization.
- Age >18 years.
- Not pregnant (confirmed by serum pregnancy test in females of reproductive potential) or breast feeding, because it is unknown what effect these drugs will have on children.
- ECOG performance status 0-2.
- AST or ATL >2x upper limit of normal unless related to CLL.
- Subject has provided written informed consent.
Who cannot join
- Subjects with autoimmune anemia or thrombocytopenia are not eligible.
- No prior cytotoxic chemotherapy. Patients with a history of steroid treatment for CLL, autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.
- Subjects with active infections requiring oral or intravenous antibiotics until resolution of the infection and completion of therapeutic antibiotics.
- Women of childbearing potential and sexually active males who refuse to use an accepted and effective method of contraception.
- Subjects with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously.
- History of HIV
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- CNS disease
- History of psychiatric disorder that would make it difficult to enroll and follow the patient on trial.
- New York Heart Classification III or IV heart disease.
- Hepatitis BsAg or Hepatitis C positive.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
This research study will look at the effects (good or bad) of administering cyclophosphamide, fludarabine, and rituximab. Clinical studies with combination therapy have shown higher response rates than using single drugs, and this study will evaluate the side effects and effectiveness of this combination.
Read the detailed description
This study is designed to expand on the highly successful combination of rituximab, fludarabine and cyclophosphamide for patients with previously untreated CLL. Responses in the range of 90-98% with 55% complete responses are reported. However, bone marrow toxicity has been a significant problem. This trial is designed to reduce the bone marrow toxicity by decreasing the doses of fludarabine and cyclophosphamide, but doubling the dose of rituximab with a maintenance dose of rituximab for up to two years, to maintain or even enhance efficacy.
- Conditions
- Chronic Lymphocytic Leukemia
- Being tested
- Fludarabine, Cyclophosphamide, Rituximab
- Keywords
- Chronic, Lymphocytic, Leukemia, Fludarabine, Cyclophosphamide, Rituximab
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Bronchiolitis Obliterans Syndrome, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Fludarabine is usually administered by IV infusion over 30 minutes or longer.
CyclophosphamideDrug
The dosage is a solution of 20 mg/mI. IV infusion over 1 hour.
RituximabDrug
First Infusion: The rituximab solution for infusion should be administered intravenously at an initial rate of 50 mg/hr. Subsequent rituximab infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.
| Study group | Role | What they receive |
|---|---|---|
| FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB | Experimental | Not described Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerability of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
The number of patients who experience any grade 3-5 toxicity.
Measured: Duration of treatment on study
Efficacy of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
The number of patients who experience a complete clinical response.
Measured: Three months after the sixth cycle (9 months)
Secondary outcomes (2)
Overall Survival Rate
The percentage of participants who are still alive.
Measured: Five years after starting rituximab, cyclophosphamide and fludarabine
Duration of Response
The length of time for which the complete response is maintained.
Measured: From complete response to the time of progressive disease, death or last clinical examination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2006 (estimated)
- Study startJun 2004
- Primary completionFeb 2008
- Study completionJan 2013
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 Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Biogen
- Responsible party
- Principal investigator, Michael Boyiadzis, University of Pittsburgh
- Investigators
- Micahel Boyiadzis, MD, Principal investigator, University of Pittsburgh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00280241
- Sponsor's protocol ID
- 03-136
- Status last verified
- Jan 2016
- First submitted
- 19 Jan 2006
- Last updated
- 4 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00280241
- Acronym / sponsor ID
- 03-136
- Conditions
- Chronic Lymphocytic Leukemia
- Keywords
- Chronic, Lymphocytic, Leukemia, Fludarabine, Cyclophosphamide, Rituximab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- Genentech, Inc., Biogen
- Study start
- Jun 2004
- Primary completion
- Feb 2008 (actual)
- Study completion
- Jan 2013 (actual)
- First posted
- 20 Jan 2006 (estimated)
- Results
- Posted 4 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study will look at the effects (good or bad) of administering cyclophosphamide, fludarabine, and rituximab. Clinical studies with combination therapy have shown higher response rates than using single drugs, and this study will evaluate the side effects and effectiveness of this combination.
Detailed description
This study is designed to expand on the highly successful combination of rituximab, fludarabine and cyclophosphamide for patients with previously untreated CLL. Responses in the range of 90-98% with 55% complete responses are reported. However, bone marrow toxicity has been a significant problem. This trial is designed to reduce the bone marrow toxicity by decreasing the doses of fludarabine and cyclophosphamide, but doubling the dose of rituximab with a maintenance dose of rituximab for up to two years, to maintain or even enhance efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Drug: Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Diagnosis of CD20 + CLL
- Peripheral blood absolute lymphocyte count of > 5,000/mm3 obtained within 2 weeks prior to randomization.
- The lymphocytosis must consist of small to moderate size lymphocytes, with ≤55% (no greater than 55%) prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically.
- Phenotypically characterized CD20 + CLL defined as: 1) the predominant population of cells share B-cell antigens with CD5 in the absence of other pan-T-celI markers (CD3, CD2, etc.); 2) B-cell expresses either kappa or lambda light chains; and 3) surface immunoglobulin (slg) with low-cell surface density expression.
- Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of CLL.
Key exclusion criteria (10 listed)
- Subjects with autoimmune anemia or thrombocytopenia are not eligible.
- No prior cytotoxic chemotherapy. Patients with a history of steroid treatment for CLL, autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.
- Subjects with active infections requiring oral or intravenous antibiotics until resolution of the infection and completion of therapeutic antibiotics.
- Women of childbearing potential and sexually active males who refuse to use an accepted and effective method of contraception.
- Subjects with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix are not eligible unless the tumor was treated with curative intent at least two years previously.
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 |
|---|---|---|
| FludarabineFludarabine is usually administered by IV infusion over 30 minutes or longer. | Drug | FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB |
| CyclophosphamideThe dosage is a solution of 20 mg/mI. IV infusion over 1 hour. | Drug | FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB |
| RituximabFirst Infusion: The rituximab solution for infusion should be administered intravenously at an initial rate of 50 mg/hr. Subsequent rituximab infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated. | Drug | FLUDARABINE, CYCLOSPHOSPHAMIDE AND RITUXIMAB |
Primary outcome
Tolerability of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
Time frame: Duration of treatment on study
The number of patients who experience any grade 3-5 toxicity.
Efficacy of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL
Time frame: Three months after the sixth cycle (9 months)
The number of patients who experience a complete clinical response.
2 secondary outcomes
Overall Survival Rate
Time frame: Five years after starting rituximab, cyclophosphamide and fludarabine
Duration of Response
Time frame: From complete response to the time of progressive disease, death or last clinical examination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2016.
- 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.
Micahel Boyiadzis, MD principal investigator
University of Pittsburgh Medical 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 Fludarabine, Cyclophosphamide and Rituximab in people with Chronic Lymphocytic Leukemia, run by University of Pittsburgh 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 23 inclusion and 10 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 4 Feb 2016. 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 4 Feb 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?
Tolerability of Rituximab, Cyclophosphamide and Fludarabine in Patients With Previously Untreated CLL/SLL (time frame: Duration of treatment on study). 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 4 Feb 2016.