Chronic Lymphocytic LeukaemiaPhase 2NCT01446900
R-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma
A Phase 2 study testing Rituximab and Cladribine in people with Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma, run by European Institute of Oncology at 1 site in Italy.
Trial summary
The objective of this study is to confirm the efficacy of the association of R-2cda in patients affected by Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma
- What is being tested?
- Rituximab and Cladribine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteItaly
- Study dates
- Jan 2011to Dec 2017
- 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
- Aged ≥ 18 years
- Patients affected by CLL / SLL
- Presence of active disease defined as the presence of one of the following:
- Disease related symptoms (weight loss >10% in the last 6 months, fever >38° C for 2 weeks without evidence of infection, or marked asthenia, or profuse sweating without evidence of infection) Massive nodes (at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Massive (at least 6 cm below left costal margin) or progressive or symptomatic splenomegaly Progressive lymphocytosis (increased >50% in 2 months) or lymphocyte doubling time < 6 months Evidence of progressive bone marrow insufficiency seen as evidence of or worsening of anemia and or thrombocytopenia Autoimmune anemia and or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
Who cannot join
- Age < 18 years
- Patients with cardiac, pulmonary, neurological, psychiatric or serious metabolic conditions not related to CLL / SLL
- Altered hepatic function (bilirubin, GOT, GPT, or gammaGT > 2 times upper limit of normal) not attributable to CLL / SLL
- Altered renal function (creatinine > 1,5 times upper limit of normal)
- Patients with serious active infections
- Pregnancy and/ or breastfeeding
Show all 11Show fewer
- Patients with positive serology for HBSAG or HBCAB without evaluation by a hepatologist
- Patients with positive serology for HIV
- Life expectancy of less than 12 months
- Not taking any other experimental drugs
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cladribine (2CdA).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Rituximab-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma
The objective of this study is to confirm the efficacy of the association of R-2cda in patients affected by Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response.
Read the detailed description
Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder characterized by the progressive accumulation of monoclonal peripheral B cells in bone marrow, peripheral blood and lymphoid tissues. Median survival is about 10 years. It is now clear that front line therapy for a patient with CLL requiring treatment should be the association of purine analogue and rituximab with or without cyclophosphamide. Concerning the choice of the purine analogue, similar results have been obtained by using cladribine instead of fludarabine. Although cladribine is less commonly used, the direct comparison between the two analogues for what concerns efficacy and toxicity, has confirmed the same profile of the two drugs. Encouraging results have been obtained using the monoclonal antibody in association with the purine analogue.
The utilization of rituximab as a maintenance therapy could improve the response in cases of persistence of minimal residual disease as well as delay the insurgence of relapses thus increasing the DFS.
The objective of this study is to confirm the efficacy of the association of R-2cda and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response. The results of this study will be compared with existing clinical results from a group of 42 pts already treated as standard with R-2cda without additional rituximab infusions.
Patients enrolled in the study will receive 4 cycles of R-2-CdA therapy. Patients, who achieve a partial response or complete response after the therapy with R- 2-CdA, will prolong therapy with Rituximab. The therapy will begin 3 months after the end of the induction therapy and patients will receive one administration every 2 months for a total of 8 administrations.
- Being tested
- Rituximab, Cladribine
- Keywords
- Rituximab, Cladribine, Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma
- Medical subject headings
- Leukemia, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera
375mg/mq, IV on day 1 of each 28 day cycle for 4 cycles. 375 mg/mq IV every 2 months for a total of 8 administrations as additional infusions for patients, who achieve a partial response or complete response after the therapy with R- 2-CdA.
CladribineDrug
Also called Litak
0,1 mg/Kg, SC from day 1 to day 5 of each 28 day cycle for 4 cycles.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab cladribine | Experimental | Not described Receives: Drug: Rituximab; Drug: Cladribine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to treatment
response will be evaluated according to Hallek criteria and definitions
Measured: at month 17
Secondary outcomes (1)
Duration of response
Duration of response Every 6 months in the first year of follow-up and every 12 months since second year until PD
Measured: Every 6 months in the first year of follow-up and every 12 months afterwards until disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study startJan 2011
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: low rate in patient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukaemiaStudies of the same condition, open and under way.
- More trials run by European Institute of OncologyThe 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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- European Institute of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giovanni Martinelli, MD, Study chair, European Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446900
- Sponsor's protocol ID
- IEO S523/110
- Other IDs
- 2010-018519-14
- Status last verified
- Dec 2017
- First submitted
- 15 Jun 2011
- Last updated
- 31 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Bertazzoni P, Rabascio C, Gigli F, Calabrese L, Radice D, Calleri A, Gregato G, Negri M, Liptrott SJ, Bassi S, Nassi L, Sammassimo S, Laszlo D, Preda L, Pruneri G, Orlando L, Martinelli G. Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients. Leuk Lymphoma. 2010 Aug;51(8):1485-93. doi: 10.3109/10428194.2010.495799.
PubMed 20578816Del Poeta G, Del Principe MI, Buccisano F, Maurillo L, Capelli G, Luciano F, Perrotti AP, Degan M, Venditti A, de Fabritiis P, Gattei V, Amadori S. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer. 2008 Jan 1;112(1):119-28. doi: 10.1002/cncr.23144.
PubMed 17999417
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rituximab-2cda and Prolongation of Therapy With Rituximab Alone in Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma
- ClinicalTrials.gov ID
- NCT01446900
- Acronym / sponsor ID
- IEO S523/110
- Keywords
- Rituximab, Cladribine, Chronic Lymphocytic Leukaemia, Small Lymphocytic Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low rate in patient accrual
- Enrolment
- 25 participants (actual)
- Lead sponsor
- European Institute of OncologyUniversity, hospital or other
- Study start
- Jan 2011
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 5 Oct 2011 (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.
The objective of this study is to confirm the efficacy of the association of R-2cda in patients affected by Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response.
Detailed description
Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder characterized by the progressive accumulation of monoclonal peripheral B cells in bone marrow, peripheral blood and lymphoid tissues. Median survival is about 10 years. It is now clear that front line therapy for a patient with CLL requiring treatment should be the association of purine analogue and rituximab with or without cyclophosphamide. Concerning the choice of the purine analogue, similar results have been obtained by using cladribine instead of fludarabine. Although cladribine is less commonly used, the direct comparison between the two analogues for what concerns efficacy and toxicity, has confirmed the same profile of the two drugs. Encouraging results have been obtained using the monoclonal antibody in association with the purine analogue.
The utilization of rituximab as a maintenance therapy could improve the response in cases of persistence of minimal residual disease as well as delay the insurgence of relapses thus increasing the DFS.
The objective of this study is to confirm the efficacy of the association of R-2cda and of evaluating the efficacy of prolongation of therapy with additional infusions of Rituximab alone in increasing and prolonging the duration of the response. The results of this study will be compared with existing clinical results from a group of 42 pts already treated as standard with R-2cda without additional rituximab infusions.
Patients enrolled in the study will receive 4 cycles of R-2-CdA therapy. Patients, who achieve a partial response or complete response after the therapy with R- 2-CdA, will prolong therapy with Rituximab. The therapy will begin 3 months after the end of the induction therapy and patients will receive one administration every 2 months for a total of 8 administrations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Rituximab cladribine | Experimental | Drug: Rituximab, Drug: Cladribine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged ≥ 18 years
- Patients affected by CLL / SLL
- Presence of active disease defined as the presence of one of the following:
- Disease related symptoms (weight loss >10% in the last 6 months, fever >38° C for 2 weeks without evidence of infection, or marked asthenia, or profuse sweating without evidence of infection) Massive nodes (at least 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy Massive (at least 6 cm below left costal margin) or progressive or symptomatic splenomegaly Progressive lymphocytosis (increased >50% in 2 months) or lymphocyte doubling time < 6 months Evidence of progressive bone marrow insufficiency seen as evidence of or worsening of anemia and or thrombocytopenia Autoimmune anemia and or thrombocytopenia that is poorly responsive to corticosteroids or other standard therapy
Key exclusion criteria (11 listed)
- Age < 18 years
- Patients with cardiac, pulmonary, neurological, psychiatric or serious metabolic conditions not related to CLL / SLL
- Altered hepatic function (bilirubin, GOT, GPT, or gammaGT > 2 times upper limit of normal) not attributable to CLL / SLL
- Altered renal function (creatinine > 1,5 times upper limit of normal)
- Patients with serious active infections
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 |
|---|---|---|
| RituximabAlso: Mabthera375mg/mq, IV on day 1 of each 28 day cycle for 4 cycles. 375 mg/mq IV every 2 months for a total of 8 administrations as additional infusions for patients, who achieve a partial response or complete response after the therapy with R- 2-CdA. | Drug | Rituximab cladribine |
| CladribineAlso: Litak0,1 mg/Kg, SC from day 1 to day 5 of each 28 day cycle for 4 cycles. | Drug | Rituximab cladribine |
Primary outcome
Response to treatment
Time frame: at month 17
response will be evaluated according to Hallek criteria and definitions
1 secondary outcome
Duration of response
Time frame: Every 6 months in the first year of follow-up and every 12 months afterwards until disease progression
Results and safety
The study was stopped early (reason given: low rate in patient accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2018.
- Background: PubMed 20578816Bertazzoni P, Rabascio C, Gigli F, Calabrese L, Radice D, Calleri A, Gregato G, Negri M, Liptrott SJ, Bassi S, Nassi L, Sammassimo S, Laszlo D, Preda L, Pruneri G, Orlando L, Martinelli G. Rituximab and subcutaneous cladribine in chronic lymphocytic leukemia for newly diagnosed and relapsed patients. Leuk Lymphoma. 2010 Aug;51(8):1485-93. doi: 10.3109/10428194.2010.495799.
- Background: PubMed 17999417Del Poeta G, Del Principe MI, Buccisano F, Maurillo L, Capelli G, Luciano F, Perrotti AP, Degan M, Venditti A, de Fabritiis P, Gattei V, Amadori S. Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia. Cancer. 2008 Jan 1;112(1):119-28. doi: 10.1002/cncr.23144.
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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.
Giovanni Martinelli, MD study chair
European Institute of Oncology
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 and Cladribine in people with Chronic Lymphocytic Leukaemia and Small Lymphocytic Lymphoma, run by European Institute of Oncology at 1 site in Italy.
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 4 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: stopped early, as of the sponsor's last update on 31 Jan 2018. 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 Italy. 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?
The study was stopped early (reason given: low rate in patient accrual). Results are not available in the source record.
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?
Response to treatment (time frame: at month 17). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01446900, which also lists 2 linked publications.
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 31 Jan 2018.