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| ID | Type | Description | Link |
|---|---|---|---|
| LLC0606 | Other Identifier | GIMEMA | |
| 2006-006185-42 | EudraCT Number |
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This is a phase I - II multicenter, non-comparative, open label study in patients with previously treated CLL aimed at defining the MTD of Lenalidomide given in combination with Fludarabine, Cyclophosphamide and at evaluating the (CR) rate of FC given in combination with the MTD of Lenalidomide (FCL).
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a phase I - II multicenter, non-comparative, open label study in patients with previously treated CLL aimed at defining the MTD of Lenalidomide given in combination with Fludarabine, Cyclophosphamide and at evaluating the (CR) rate of FC given in combination with the MTD of Lenalidomide (FCL).
All patients will receive six monthly courses of FCL schedule consisting of three days of Fludarabine and Cyclophosphamide administration (d1-d3) combined with 14 days of Lenalidomide administration (d1-d14).
After completion of study treatment, patients are followed periodically for up to 18 months.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | All patients will receive six monthly courses of FCL schedule consisting of three days of Fludarabine and Cyclophosphamide administration (d1-d3) combined with 14 days of Lenalidomide administration (d1-d14). | ||
| Fludarabine phosphate | Drug | All patients will receive six monthly courses of FCL schedule consisting of three days of Fludarabine and Cyclophosphamide administration (d1-d3) combined with 14 days of Lenalidomide administration (d1-d14). | ||
| Lenalidomide | Drug | All patients will receive six monthly courses of FCL schedule consisting of three days of Fludarabine and Cyclophosphamide administration (d1-d3) combined with 14 days of Lenalidomide administration (d1-d14). In the first phase of the study, the dose of Lenalidomide given with FC will be gradually escalated to reach the MTD. In the second phase of the study, FC will be given in combination with the Lenalidomide escalated to the MTD or the maximum planned dose. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose of Lenalidomide (Phase I) | Maximum tolerated dose of lenalidomide given in combination with fludarabine. | The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level. |
| Overall Complete Response (CR) Rate (Phase II) | Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. | After 6 months from study entry (end of treatment). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Reaching Disease-free Survival (DSF) Overall | Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. | After 6 months from study entry (end of treatment) |
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Inclusion criteria:
Age >=18 years.
Able to adhere to the study visit schedule and other protocol requirements.
Patients with advanced stage or progressive CLL (NCI criteria) and relapsed or refractory disease.
No more than 2 previous different treatment lines.
No treatment with Campath-1H in the previous 6 months.
Disease-free of prior malignancies for >=5 years, with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
All previous cancer therapy, including chemotherapy, immunotherapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study.
ECOG performance status of <=2 at study entry.
Laboratory test results within these ranges:
Able to take low molecular weight heparin or in alternative, low- fixed-dose warfarin or, in alternative, low-dose aspirin.
Able to understand and voluntarily sign the informed consent form.
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10 - 14 days prior to therapy and repeated within 24 hours of starting study. FCBP must agree to use two reliable forms of contraception for at least 28 days before starting study drug; while participating in the study; and for at least 4 weeks after discontinuation from the study.
Females must agree to abstain from breastfeeding during study participation and for at least 28 days after discontinuation from the study.
Males must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 4 weeks following discontinuation.
(Other details regarding pregnancy tests and contraception are reported in the chapter "Eligibility Criteria" within the study protocol).
Exclusion criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roberto Foa, MD | Universita Degli Studi "La Sapeinza" | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Unità Operativa Ematologia 1 - Università degli Studi di Bari | Bari | 70010 | Italy | |||
| Istituto di Ematologia e Oncologia Medica "Lorenzo e A. Seragnoli" - Università degli Studi di Bologna - Policlinico S. Orsola - Malpighi |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27881039 | Derived | Mauro FR, Carella AM, Molica S, Paoloni F, Liberati AM, Zaja F, Belsito V, Cortellezzi A, Rizzi R, Tosi P, Spriano M, Ferretti A, Nanni M, Marinelli M, De Propris MS, Orlando SM, Vignetti M, Cuneo A, Guarini AR, Foa R. Fludarabine, cyclophosphamide and lenalidomide in patients with relapsed/refractory chronic lymphocytic leukemia. A multicenter phase I-II GIMEMA trial. Leuk Lymphoma. 2017 Jul;58(7):1640-1647. doi: 10.1080/10428194.2016.1258698. Epub 2016 Nov 23. |
| Label | URL |
|---|---|
| GIMEMA Foundation Website | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase I-II Lenalidomide | The phase I of the study, carried out at a single center (Hematology, Sapienza University of Rome) was focused at defining the MTD of lenalidomide given in combination with the FC regimen according to a 3 + 3 patient design. During the first course of treatment, lenalidomide was given to all patients at the starting dose of 2.5 mg daily (d1-d14). For the subsequent courses, the dose of lenalidomide was progressively escalated at each course, according to a 3 + 3 patient design. In 3 cohorts of 3 patients each, a daily dose of 5, 10, and 15 mg of lenalidomide was tested unless a dose limiting toxicity (DLT) was experienced. The presence of a persistent and severe hematologic toxicity, grade 2 tumor lysis syndrome (TLS), grade 3 tumor flare reaction (TFR), or other grade 3 toxicities was defined as DLT. In the second phase of the study, FC was given in combination with lenalidomide escalated from 2.5 mg to reach the MTD or the maximum planned dose of 15 mg. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase I |
|
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| Toxicity as Assessed by NCI CTCAE v3.0 |
Data from all subjects who receive any study drug will be included in the safety analyses. |
| At 24 months from study entry (end of follow-up) |
| Number of Patients With Severe Infections | Severe infection requiring more than 2 weeks of antibiotic therapy. | At 24 months from study entry (end of follow-up) |
| Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.). | After 6 months from study entry (end of treatment). |
| Bologna |
| Italy |
| Azienda Ospedaliera Pugliese Ciaccio | Catanzaro | 88100 | Italy |
| Sez.Ematologia e Dip. scienze Biomediche Arcispedale S. Anna | Ferrara | 44100 | Italy |
| Clinica Ematologica - Università degli Studi | Genova | Italy |
| Divisione di Ematologia Ospedale "Santa Maria Goretti" | Latina | Italy |
| Istituto Scientifico Romagnoli per lo Studio e la Cura dei Tumori- IRST | Meldola | Italy |
| Divisione di Ematologia - Azienda Ospedaliera Ospedali Riuniti "Papardo Piemonte" | Messina | Italy |
| UO Centro Trapianti di Midollo - IRCCS Ospedale Maggiore Policlinico | Milan | Italy |
| (SA) U.O. di Oncoematologia di Nocera Inferiore-plesso ospedaliero "A. Tortora" di Pagani del DEA Nocera-Pagani | Nocera Inferiore | Italy |
| Università degli Studi di Padova - Ematologia ed Immunologia Clinica | Padova | Italy |
| U.O. Ematologia Clinica - Azienda USL di Pescara | Pescara | Italy |
| Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza | Piacenza | Italy |
| Ospedale S. M. delle Croci | Ravenna | I-48100 | Italy |
| Azienda Ospedaliera Bianchi Melacrino Morelli | Reggio Calabria | 89100 | Italy |
| Ospedale "Infermi" | Rimini | Italy |
| Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia | Roma | Italy |
| Universita Degli Studi "La Sapeinza" | Rome | 00161 | Italy |
| Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore | Rome | 00168 | Italy |
| U.O.C. Ematologia - Ospedale S.Eugenio | Rome | Italy |
| U.O. Ematologia, Azienda Ospedaliera Universitaria Senese | Siena | 53100 | Italy |
| SS.C. di Oncoematologia - Dipartimento di Medicina Clinica e Sperimentale - Azienda Ospedaliera - S. Maria Di Terni | Terni | Italy |
| Clinica Ematologica - Policlinico Universitario | Udine | Italy |
| COMPLETED |
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| NOT COMPLETED |
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| Phase II |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I-II Lenalidomide | The phase I of the study, carried out at a single center (Hematology, Sapienza University of Rome) was focused at defining the MTD of lenalidomide given in combination with the FC regimen according to a 3 + 3 patient design. During the first course of treatment, lenalidomide was given to all patients at the starting dose of 2.5 mg daily (d1-d14). For the subsequent courses, the dose of lenalidomide was progressively escalated at each course, according to a 3 + 3 patient design. In 3 cohorts of 3 patients each, a daily dose of 5, 10, and 15 mg of lenalidomide was tested unless a dose limiting toxicity (DLT) was experienced. The presence of a persistent and severe hematologic toxicity, grade 2 tumor lysis syndrome (TLS), grade 3 tumor flare reaction (TFR), or other grade 3 toxicities was defined as DLT. In the second phase of the study, FC was given in combination with lenalidomide escalated from 2.5 mg to reach the MTD or the maximum planned dose of 15 mg. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
| |||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose of Lenalidomide (Phase I) | Maximum tolerated dose of lenalidomide given in combination with fludarabine. | Posted | Number | number of patients without DLT | The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level. |
|
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| Primary | Overall Complete Response (CR) Rate (Phase II) | Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. | 7 patients coming from the phase I + 33 patients enrolled from the phase II. The whole population of phase II part of the trial is composed of a total of 40 patients. | Posted | Number | percentage of patients in CR | After 6 months from study entry (end of treatment). |
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| Secondary | Number of Patients Reaching Disease-free Survival (DSF) Overall | Response will be assessed by clinical examination, peripheral blood, bone marrow aspirate and biopsy, radiographic evaluation. Response will be evaluated at three different levels: clinical, cytometric and molecular. | Posted | Number | 95% Confidence Interval | percentage of participants on DFS | After 6 months from study entry (end of treatment) |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Toxicity as Assessed by NCI CTCAE v3.0 | Data from all subjects who receive any study drug will be included in the safety analyses. | Fourteen (35%) patients have died. | Posted | Number | Participants who died during the study | At 24 months from study entry (end of follow-up) |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Number of Patients With Severe Infections | Severe infection requiring more than 2 weeks of antibiotic therapy. | Posted | Number | participants with severe infecitons | At 24 months from study entry (end of follow-up) |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.). | Posted | Number | percentage of participants | After 6 months from study entry (end of treatment). |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase I-II Lenalidomide | The phase I of the study, carried out at a single center (Hematology, Sapienza University of Rome) was focused at defining the MTD of lenalidomide given in combination with the FC regimen according to a 3 + 3 patient design. During the first course of treatment, lenalidomide was given to all patients at the starting dose of 2.5 mg daily (d1-d14). For the subsequent courses, the dose of lenalidomide was progressively escalated at each course, according to a 3 + 3 patient design. In 3 cohorts of 3 patients each, a daily dose of 5, 10, and 15 mg of lenalidomide was tested unless a dose limiting toxicity (DLT) was experienced. The presence of a persistent and severe hematologic toxicity, grade 2 tumor lysis syndrome (TLS), grade 3 tumor flare reaction (TFR), or other grade 3 toxicities was defined as DLT. In the second phase of the study, FC was given in combination with lenalidomide escalated from 2.5 mg to reach the MTD or the maximum planned dose of 15 mg. | 14 | 40 | 8 | 40 | 0 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchopneumonia | Infections and infestations | Non-systematic Assessment |
| ||
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
| ||
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Multi-organi failure | General disorders | Non-systematic Assessment |
| ||
| Supraventricular tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Craniocerebral injury | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| Pancytopenia | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Non-systematic Assessment |
| ||
| Intestinal obstruction | General disorders | Non-systematic Assessment |
| ||
| myelodisplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alfonso Piciocchi | GIMEMA | +39 06 70390513 | a.piciocchi@gimema.it |
| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| D000077269 | Lenalidomide |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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