Advanced Refractory Chronic Lymphocytic LeukemiaPhase 2NCT00892827
Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia
A Phase 2 study testing Rituximab (Mabthera) , FFP (Fresh Frozen Plasma) in people with Advanced Refractory Chronic Lymphocytic Leukemia, run by Wolfson Medical Center at 1 site in Israel.
Trial summary
Chronic lymphocytic leukemia (CLL), an indolent disease of mature-looking B lymphocytes, is the most common leukemia in Israel and the Western world. The disease is associated with considerable morbidity and mortality, and is currently incurable. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Refractory Chronic Lymphocytic Leukemia
- What is being tested?
- Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteIsrael
- Study dates
- Apr 2009to Dec 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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: advanced (Rai stage ≥2 or symptomatic stage 1) CLL Resistant to or relapsing after treatment with Fludarabine and/or Rituximab
- Lymphocyte count of 100,000 cells/mcl or higher.
- Time from last anti-leukemia treatment: 1 month or more
- Age: male or female over 18 years of age.
- Informed consent - obtained
Who cannot join
- Lack of one or more of the inclusion criteria
- Known sensitivity to human plasma
- Known sensitivity to Rituximab (Mabthera)
- Active second malignant disease (other than non-melanoma skin cancer) < 2 years prior to the study
- Active infectious disease < 1 month prior to the study
- Hepatitis B serology: Hepatitis B surface antigen - positive
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- Renal function: Creatinin > 3 mg/dL
- Liver function: Liver enzymes less than x2 of the normal values
- Performance status: ECOG performance status 4
- Use of other investigational agent < 30 days ago
- Known poor adherence to treatment plan
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Wolfson MC
Holon, Holon, 58100
Abraham Klepfish, MD, 972-35028778, klepfish@wolfson.health.gov.il
Goldstein Daniela, MD
About this study
Official title: The Efficacy and Safety of Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia. Single-arm Phase II Study. Analysis of Complement Activation Pathways.
Chronic lymphocytic leukemia (CLL), an indolent disease of mature-looking B lymphocytes, is the most common leukemia in Israel and the Western world. The disease is associated with considerable morbidity and mortality, and is currently incurable. Rituximab (Mabthera) is a chimeric monoclonal antibody directed against CD20 antigen, present exclusively on B lymphocytes. Treatment with Rituximab is widely used in indolent B cell malignancies. However, the administration of Rituximab in CLL patients yields less successful results than in other indolent B cell malignancies, and even responding patients may become refractory. We hypothesized that the abnormalities in the complement system identified in CLL underlie the suboptimal response to Rituximab, since complement-dependent cell cytotoxicity is a major mechanism of Rituximab action. Following patient consent and Institutional Review Board approval, standard-dose Rituximab (375 mg/m2) will be administered, preceded by 2 units of FFP. This treatment will be repeated every 1-2 weeks for 4-6 cycles. The clinical and laboratory parameters, as well as adverse drug events, will be monitored.
Read the detailed description
Indolent B cell Non-Hodgkin's lymphoma patients show good responses to Rituximab, administered either alone or preferably with standard chemotherapy. The response to Rituximab of patients with CLL is inferior in comparison to other indolent B cell malignancies. The therapeutic approach of combining treatments with Rituximab and fresh frozen plasma (FFP) used by us first in one case and following the impressive response - in additional 2 patients, was undertaken on the basis of two observations.
We assumed, that the addition of FFP to Rituximab treatment would increase and/or restore the efficacy of Rituximab in advanced CLL patients that are resistant to therapy by correcting their abnormal complement system thus allowing improved complement activation and increase anti-leukemic activity.
The major aims of the study are: (1) To establish the efficacy of the combination of FFP and RTX as determined by response rate. (2) To elucidate the effector mechanism responsible for the efficacy of the FFP-Rituximab combination. The secondary aims of the study are (1) To establish the response duration of the combination of FFP and RTX as determined by time to progression. and time to re treatment (2) To determine the safety of the combined treatment.
The study is designed as a single-arm, phase II study evaluating the efficacy and safety of combined treatment with FFP and RTX in advanced refractory chronic lymphocytic leukemia, along with an analysis of the complement system associated parameters.
- Being tested
- Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)
- Keywords
- Rituximab, Mabthera, FFP, Fresh Frozen Plasma, CLL, Complement, Response, Overall response rate of FFP+Rituximab combined therapy, Analysis of complement activation pathways prior to, during and, after the study treatment., Time to disease progression, Time to re-treatment (See Appendix I)., Safety of the combination treatment of FFP and RTX.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)Drug
Rituximab (375 mg/m2) with FFP will be given every two weeks
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study | Experimental | Rituximab Receives: Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To establish the efficacy of the combination of FFP and RTX as determined by response rate. Complete/Partial Response includes parameters: Physical Exam,Symptoms,Lymphocytes, Neutrophils, Platelets,Hb (g/dL),Bone marrow lymph
Measured: 3 months
Secondary outcomes (3)
Time to disease progression
Measured: 6-12 months
Time to re-treatment
Measured: 6-12 months
Safety of the combination treatment of FFP and RTX
Measured: 6-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2009 (estimated)
- Study startApr 2009
- Primary completionJul 2009 (estimated)
- Study completionDec 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Refractory 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wolfson Medical Center
- Sponsor type
- Other government
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00892827
- Sponsor's protocol ID
- AK- 01
- Status last verified
- Sep 2010
- First submitted
- 4 May 2009
- Last updated
- 14 Sep 2010
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Combined Treatment With Fresh Frozen Plasma and Rituximab (Mabthera) in Patients With Advanced Refractory Chronic Lymphocytic Leukemia. Single-arm Phase II Study. Analysis of Complement Activation Pathways.
- ClinicalTrials.gov ID
- NCT00892827
- Acronym / sponsor ID
- AK- 01
- Keywords
- Rituximab, Mabthera, FFP, Fresh Frozen Plasma, CLL, Complement, Response, Overall response rate of FFP+Rituximab combined therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Wolfson Medical CenterOther government
- Study start
- Apr 2009
- Primary completion
- Jul 2009 (estimated)
- Study completion
- Dec 2010 (estimated)
- First posted
- 5 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic lymphocytic leukemia (CLL), an indolent disease of mature-looking B lymphocytes, is the most common leukemia in Israel and the Western world. The disease is associated with considerable morbidity and mortality, and is currently incurable. Rituximab (Mabthera) is a chimeric monoclonal antibody directed against CD20 antigen, present exclusively on B lymphocytes. Treatment with Rituximab is widely used in indolent B cell malignancies. However, the administration of Rituximab in CLL patients yields less successful results than in other indolent B cell malignancies, and even responding patients may become refractory. We hypothesized that the abnormalities in the complement system identified in CLL underlie the suboptimal response to Rituximab, since complement-dependent cell cytotoxicity is a major mechanism of Rituximab action. Following patient consent and Institutional Review Board approval, standard-dose Rituximab (375 mg/m2) will be administered, preceded by 2 units of FFP. This treatment will be repeated every 1-2 weeks for 4-6 cycles. The clinical and laboratory parameters, as well as adverse drug events, will be monitored.
Detailed description
Indolent B cell Non-Hodgkin's lymphoma patients show good responses to Rituximab, administered either alone or preferably with standard chemotherapy. The response to Rituximab of patients with CLL is inferior in comparison to other indolent B cell malignancies. The therapeutic approach of combining treatments with Rituximab and fresh frozen plasma (FFP) used by us first in one case and following the impressive response - in additional 2 patients, was undertaken on the basis of two observations.
We assumed, that the addition of FFP to Rituximab treatment would increase and/or restore the efficacy of Rituximab in advanced CLL patients that are resistant to therapy by correcting their abnormal complement system thus allowing improved complement activation and increase anti-leukemic activity.
The major aims of the study are: (1) To establish the efficacy of the combination of FFP and RTX as determined by response rate. (2) To elucidate the effector mechanism responsible for the efficacy of the FFP-Rituximab combination. The secondary aims of the study are (1) To establish the response duration of the combination of FFP and RTX as determined by time to progression. and time to re treatment (2) To determine the safety of the combined treatment.
The study is designed as a single-arm, phase II study evaluating the efficacy and safety of combined treatment with FFP and RTX in advanced refractory chronic lymphocytic leukemia, along with an analysis of the complement system associated parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm Study | Experimental | Drug: Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)Rituximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis: advanced (Rai stage ≥2 or symptomatic stage 1) CLL Resistant to or relapsing after treatment with Fludarabine and/or Rituximab
- Lymphocyte count of 100,000 cells/mcl or higher.
- Time from last anti-leukemia treatment: 1 month or more
- Age: male or female over 18 years of age.
- Informed consent - obtained
Key exclusion criteria (11 listed)
- Lack of one or more of the inclusion criteria
- Known sensitivity to human plasma
- Known sensitivity to Rituximab (Mabthera)
- Active second malignant disease (other than non-melanoma skin cancer) < 2 years prior to the study
- Active infectious disease < 1 month prior to the study
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 |
|---|---|---|
| Rituximab (Mabthera) , FFP (Fresh Frozen Plasma)Rituximab (375 mg/m2) with FFP will be given every two weeks | Drug | Single Arm Study |
Primary outcome
To establish the efficacy of the combination of FFP and RTX as determined by response rate. Complete/Partial Response includes parameters: Physical Exam,Symptoms,Lymphocytes, Neutrophils, Platelets,Hb (g/dL),Bone marrow lymph
Time frame: 3 months
3 secondary outcomes
Time to disease progression
Time frame: 6-12 months
Time to re-treatment
Time frame: 6-12 months
Safety of the combination treatment of FFP and RTX
Time frame: 6-12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2010.
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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.
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 Rituximab (Mabthera) , FFP (Fresh Frozen Plasma) in people with Advanced Refractory Chronic Lymphocytic Leukemia, run by Wolfson Medical Center at 1 site in Israel.
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 5 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 14 Sep 2010. 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 Israel. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To establish the efficacy of the combination of FFP and RTX as determined by response rate. Complete/Partial Response includes parameters: Physical Exam,Symptoms,Lymphocytes, Neutrophils, Platelets,Hb (g/dL),Bone marrow lymph (time frame: 3 months). 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 14 Sep 2010.