LeukemiaPhase 2LLC0405NCT00462332
Fludarabine and Alemtuzumab or Cyclophosphamide Followed by Peripheral Blood Stem Cell Transplant or Alemtuzumab in Treating Patients With Advanced or Progressive Chronic Lymphocytic Leukemia
A Phase 2 study testing Fludarabine, Campath and Transplant in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 23 sites in Italy.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Read more about this study
- Who is it for?
- Ages Up to 60 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Fludarabine, Campath and Transplant
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 23 sitesItaly
- Study dates
- May 2007to Jun 2011
- 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 Up to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Diagnosis of chronic lymphocytic leukemia (CLL)
- Advanced or progressive disease with ≥ 2 active clinical signs
PATIENT CHARACTERISTICS:
- Fertile patients must use adequate contraception
- No positive Coomb's test with signs of hemolysis
- No active infection
- No uncontrolled severe disease
- No known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
- No other malignancies within the past 2 years except for adequately treated malignancies
- No significant traumatic injury within the past 4 weeks
- No coexisting medical or psychological condition that would limit study compliance
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior treatment for CLL
- No major surgery within the past 4 weeks
- No prior chemotherapy
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
Italy23 sites
S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
Alessandria
Universita Degli Studi di Bari
Bari, 70124
Universita Cattolica del Sacro Cuore - Campobasso
Campobasso, 86100
Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
Catania, 95124
Ospedale Regionale A. Pugliese
Catanzaro, 88100
Ospedale Civile Cosenza
Cosenza, 87100
Universita di Ferrara
Ferrara, 44100
Azienda Ospedaliera di Firenze
Florence, 50011
Ospedale San Martino
Genova, 16132
ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
Lecce
Azienda Ospedaliera Papardo
Messina
Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
Messina
Ospedale Maggiore Policlinico
Milan, 20122
Azienda Ospedaliera - Universitaria di Modena
Modena, 41100
U.O. Ematologia Clinica - Azienda USL di Pescara
Pescara
Azienda Ospedaliera Bianchi Melacrino Morelli
Reggio Calabria, 89100
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, 00133
Ospedale Sant' Eugenio
Rome, 00144
Università Degli Studi "La Sapienza"
Rome, 00161
Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
Rome, 00168
U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
Siena
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, 10126
Policlinico Universitario Udine
Udine, 33100
About this study
Official title: Phase II Pilot Trial to Evaluate the Efficacy of a Combined Therapy Approach for Young CLL Patients With Advanced and Progressive Disease Stratified According to the Biological Prognostic Features
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. A peripheral stem cell transplant using stem cells from the patient or a donor may replace the patient's immune cells that were destroyed by chemotherapy.
PURPOSE: This phase II trial is studying how well giving fludarabine together with alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplant or alemtuzumab works in treating patients with advanced or progressive chronic lymphocytic leukemia.
Read the detailed description
OBJECTIVES:
Primary
- Determine the antitumor activity of induction therapy comprising fludarabine phosphate with either alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplantation or alemtuzumab in patients with advanced or progressive chronic lymphocytic leukemia.
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine the length of survival, event-free survival, and disease-free survival of patients treated with this regimen.
- Evaluate the relationship between different clinical and biological disease characteristics, therapeutic response, and survival.
OUTLINE: This is a pilot, multicenter study. Patients are stratified according to biological risk profile (high vs low risk).
- Group 1 (high-risk patients):
- Induction therapy: Patients receive fludarabine phosphate IV and alemtuzumab IV on days 1-3. Treatment repeats for 4 courses.
Patients with no response (no good clinical partial response, steady disease, or progressive disease) after induction therapy are removed from the study. Other patients proceed to post-induction therapy based on response to induction therapy.
- Post-induction therapy:
- Complete clinical, cytometric, and molecular response: Patients undergo peripheral blood stem cell (PBSC) mobilization with cytarabine IV twice daily on days 1-3 and filgrastim (G-CSF) followed by no further therapy.
- Response to induction therapy and evidence of residual disease (complete clinical and cytometric response with molecular evidence of disease; complete clinical response only; or good clinical partial response): Patients without an HLA familial matched donor undergo PBSC mobilization with cytarabine IV twice daily on days 1-3 and G-CSF. Patients with sufficient harvested autologous PBSCs undergo autologous PBSC transplantation (with BEAM conditioning regimen [carmustine, etoposide, cytarabine, and melphalan]). Patients without sufficient harvested
- PBSCs receive alemtuzumab subcutaneously (SC) weekly for 6 weeks. Patients who do not achieve molecular remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment. Patients with an HLA familial matched
- undergo reduced-intensity allogeneic stem cell transplantation (with cyclophosphamide, thiotepa, and fludarabine phosphate as conditioning regimen).
- Group 2 (low-risk patients):
- Induction therapy: Patients receive fludarabine phosphate and cyclophosphamide on days 1-3. Treatment repeats every month for 4 courses. Patients achieving at least a partial response receive 2 additional courses.
Patients achieving complete clinical response with cytometric and molecular response; complete clinical response with a cytometric response; or complete clinical response after completion of induction therapy (i.e., partial response or greater) receive no further treatment. Patients with no response or disease progression proceed to post-induction therapy.
- Post-induction therapy: Patients receive alemtuzumab SC weekly for 6 weeks. Patients who do not achieve complete remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
- Conditions
- Leukemia
- Being tested
- Fludarabine, Campath, Transplant
- Keywords
- 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.
FludarabineDrug
Induction therapy
CampathDrug
Induction therapy
TransplantProcedure or surgery
Post-induction therapy
CampathDrug
Post-induction therapy
FludarabineDrug
Induction therapy
CampathDrug
Induction therapy
CampathDrug
Post-induction therapy
| Study group | Role | What they receive |
|---|---|---|
| High risk patientes | Experimental | Category of risk will be defined according to biological features. Receives: Drug: Fludarabine; Drug: Campath; Procedure: Transplant |
| Low risk patients | Experimental | Category of risk will be defined according to biological features. Receives: Drug: Fludarabine; Drug: Campath |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Complete Response
- Normal clinical or X-ray examination (lymph nodes, liver, spleen)
- No symptoms
- Lymphocytes higher or equal to 4.0 per 10^9/L
- Neutrophils lower or equal to 1.5 per 10^9/L
- Platelets >100 per 10^9/L
- Hb >11.0 g/dL
- Bone marrow lymphs according to age, lymphocytes <30%, no nodules.
Measured: At 2 years from study entry
Secondary outcomes (4)
Toxicity
Number of AEs and SAEs
Measured: At 2 years from study entry
Length of Survival
Measured: At 2 years and a half from study entry
Event-free Survival
Measured: At 2 years from study entry
Disease-free Survival
Measured: At 2 years from study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startMay 2007
- Primary completionJun 2011
- Study completionJun 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 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'Adulto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roberto Foa, MD, Principal investigator, Universita Degli Studi "La Sapeinza"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462332
- Sponsor's protocol ID
- LLC0405
- Other IDs
- LLC0405, 2005-002476-15, 2005
- Acronym
- LLC0405
- Status last verified
- Aug 2013
- First submitted
- 18 Apr 2007
- Last updated
- 6 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Pilot Trial to Evaluate the Efficacy of a Combined Therapy Approach for Young CLL Patients With Advanced and Progressive Disease Stratified According to the Biological Prognostic Features
- ClinicalTrials.gov ID
- NCT00462332
- Acronym / sponsor ID
- LLC0405 / LLC0405
- Conditions
- Leukemia
- Keywords
- stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Gruppo Italiano Malattie EMatologiche dell'AdultoUniversity, hospital or other
- Study start
- May 2007
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 19 Apr 2007 (estimated)
- Results
- Posted 30 Jul 2013
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, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. A peripheral stem cell transplant using stem cells from the patient or a donor may replace the patient's immune cells that were destroyed by chemotherapy.
PURPOSE: This phase II trial is studying how well giving fludarabine together with alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplant or alemtuzumab works in treating patients with advanced or progressive chronic lymphocytic leukemia.
Detailed description
OBJECTIVES:
Primary
- Determine the antitumor activity of induction therapy comprising fludarabine phosphate with either alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplantation or alemtuzumab in patients with advanced or progressive chronic lymphocytic leukemia.
Secondary
- Determine the toxicity of this regimen in these patients.
- Determine the length of survival, event-free survival, and disease-free survival of patients treated with this regimen.
- Evaluate the relationship between different clinical and biological disease characteristics, therapeutic response, and survival.
OUTLINE: This is a pilot, multicenter study. Patients are stratified according to biological risk profile (high vs low risk).
- Group 1 (high-risk patients):
- Induction therapy: Patients receive fludarabine phosphate IV and alemtuzumab IV on days 1-3. Treatment repeats for 4 courses.
Patients with no response (no good clinical partial response, steady disease, or progressive disease) after induction therapy are removed from the study. Other patients proceed to post-induction therapy based on response to induction therapy.
- Post-induction therapy:
- Complete clinical, cytometric, and molecular response: Patients undergo peripheral blood stem cell (PBSC) mobilization with cytarabine IV twice daily on days 1-3 and filgrastim (G-CSF) followed by no further therapy.
- Response to induction therapy and evidence of residual disease (complete clinical and cytometric response with molecular evidence of disease; complete clinical response only; or good clinical partial response): Patients without an HLA familial matched donor undergo PBSC mobilization with cytarabine IV twice daily on days 1-3 and G-CSF. Patients with sufficient harvested autologous PBSCs undergo autologous PBSC transplantation (with BEAM conditioning regimen [carmustine, etoposide, cytarabine, and melphalan]). Patients without sufficient harvested
- PBSCs receive alemtuzumab subcutaneously (SC) weekly for 6 weeks. Patients who do not achieve molecular remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment. Patients with an HLA familial matched
- undergo reduced-intensity allogeneic stem cell transplantation (with cyclophosphamide, thiotepa, and fludarabine phosphate as conditioning regimen).
- Group 2 (low-risk patients):
- Induction therapy: Patients receive fludarabine phosphate and cyclophosphamide on days 1-3. Treatment repeats every month for 4 courses. Patients achieving at least a partial response receive 2 additional courses.
Patients achieving complete clinical response with cytometric and molecular response; complete clinical response with a cytometric response; or complete clinical response after completion of induction therapy (i.e., partial response or greater) receive no further treatment. Patients with no response or disease progression proceed to post-induction therapy.
- Post-induction therapy: Patients receive alemtuzumab SC weekly for 6 weeks. Patients who do not achieve complete remission after 6 weeks of alemtuzumab receive 6 additional weeks of treatment.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High risk patientes | Experimental | Drug: Fludarabine, Drug: Campath, Procedure: TransplantCategory of risk will be defined according to biological features. |
| Low risk patients | Experimental | Drug: Fludarabine, Drug: CampathCategory of risk will be defined according to biological features. |
Who may qualify
- Ages
- Up to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
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 |
|---|---|---|
| FludarabineInduction therapy | Drug | High risk patientes |
| CampathInduction therapy | Drug | High risk patientes |
| TransplantPost-induction therapy | Procedure or surgery | High risk patientes |
| CampathPost-induction therapy | Drug | High risk patientes |
| FludarabineInduction therapy | Drug | Low risk patients |
| CampathInduction therapy | Drug | Low risk patients |
| CampathPost-induction therapy | Drug | Low risk patients |
Primary outcome
Number of Patients With Complete Response
Time frame: At 2 years from study entry
* Normal clinical or X-ray examination (lymph nodes, liver, spleen) * No symptoms * Lymphocytes higher or equal to 4.0 per 10^9/L * Neutrophils lower or equal to 1.5 per 10^9/L * Platelets >100 per 10^9/L * Hb >11.0 g/dL * Bone marrow lymphs according to age, lymphocytes <30%, no nodules.
4 secondary outcomes
Toxicity
Time frame: At 2 years from study entry
Length of Survival
Time frame: At 2 years and a half from study entry
Event-free Survival
Time frame: At 2 years from study entry
Disease-free Survival
Time frame: At 2 years from study entry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- GIMEMA Foundation WebsiteLink 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.
Roberto Foa, MD principal investigator
Universita Degli Studi "La Sapeinza"
23 sites 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, Campath and Transplant in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 23 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 6 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites 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?
Yes. Results are posted in the registry (first posted 30 Jul 2013). 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?
Number of Patients With Complete Response (time frame: At 2 years from study entry). 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 6 Sep 2013.