Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Lenalidomide, Fludarabine & Cyclophosphamide in Advanced Chronic Lymphocytic Leukemia Not Responding to Therapy (LLC0606)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00727415
Recruitment Status : Completed
First Posted : August 4, 2008
Results First Posted : January 21, 2019
Last Update Posted : January 21, 2019
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Lymphocytic Leukemia
Interventions Drug: Cyclophosphamide
Drug: Fludarabine phosphate
Drug: Lenalidomide
Enrollment 42
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description

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.

Period Title: Phase I
Started 9
Completed 7
Not Completed 2
Reason Not Completed
Dose Limiting Toxicity             2
Period Title: Phase II
Started 33
Completed 33
Not Completed 0
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 40 participants
66
(47 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants
Female
10
  25.0%
Male
30
  75.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Italy Number Analyzed 40 participants
40
1.Primary Outcome
Title Maximum Tolerated Dose of Lenalidomide (Phase I)
Hide Description Maximum tolerated dose of lenalidomide given in combination with fludarabine.
Time Frame The MTD of Lenalinomide will be evaluated during the two courses given with the escalated dose of Lenalinomide defined by the respective dose level.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: number of patients without DLT
Dose level 1 - 5 mg 6
Dose level 2 - 10 mg 1
2.Primary Outcome
Title Overall Complete Response (CR) Rate (Phase II)
Hide Description 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.
Time Frame After 6 months from study entry (end of treatment).
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: percentage of patients in CR
22.5
3.Secondary Outcome
Title Number of Patients Reaching Disease-free Survival (DSF) Overall
Hide Description 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.
Time Frame After 6 months from study entry (end of treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants on DFS
35.33
(22.71 to 54.95)
4.Secondary Outcome
Title Toxicity as Assessed by NCI CTCAE v3.0
Hide Description Data from all subjects who receive any study drug will be included in the safety analyses.
Time Frame At 24 months from study entry (end of follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
Fourteen (35%) patients have died.
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: Participants who died during the study
14
5.Secondary Outcome
Title Number of Patients With Severe Infections
Hide Description Severe infection requiring more than 2 weeks of antibiotic therapy.
Time Frame At 24 months from study entry (end of follow-up)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: participants with severe infecitons
2
6.Secondary Outcome
Title Correlation Between Complete Response (CR) and Baseline Biologic Parameters (i.e., IgHV, CD38, Etc.).
Hide Description [Not Specified]
Time Frame After 6 months from study entry (end of treatment).
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 42
Measure Type: Number
Unit of Measure: percentage of participants
CR according to IgHV mutated 28.00
CR according to CD19+/CD38+, <30% 33.33
CR according to CD19+/CD38+, >30% 16.67
CR according to deletion 11q and 17p, absent 31.82
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I-II Lenalidomide
Hide Arm/Group Description

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.

All-Cause Mortality
Phase I-II Lenalidomide
Affected / at Risk (%)
Total   14/40 (35.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Phase I-II Lenalidomide
Affected / at Risk (%) # Events
Total   8/40 (20.00%)    
Blood and lymphatic system disorders   
Febrile neutropenia *  2/40 (5.00%)  3
Pancytopenia *  1/40 (2.50%)  1
Cardiac disorders   
Supraventricular tachycardia *  1/40 (2.50%)  1
Atrial fibrillation *  1/40 (2.50%)  1
General disorders   
Multi-organi failure *  1/40 (2.50%)  1
Intestinal obstruction *  1/40 (2.50%)  1
Infections and infestations   
Bronchopneumonia *  2/40 (5.00%)  2
Injury, poisoning and procedural complications   
Craniocerebral injury *  1/40 (2.50%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Squamous cell carcinoma of skin *  1/40 (2.50%)  1
myelodisplastic syndrome *  1/40 (2.50%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnoea *  1/40 (2.50%)  1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I-II Lenalidomide
Affected / at Risk (%) # Events
Total   0/40 (0.00%)    
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Alfonso Piciocchi
Organization: GIMEMA
Phone: +39 06 70390513
EMail: a.piciocchi@gimema.it
Layout table for additonal information
Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT00727415     History of Changes
Other Study ID Numbers: LLC0606
LLC0606 ( Other Identifier: GIMEMA )
2006-006185-42 ( EudraCT Number )
First Submitted: August 1, 2008
First Posted: August 4, 2008
Results First Submitted: November 8, 2017
Results First Posted: January 21, 2019
Last Update Posted: January 21, 2019