T-cell Non-Hodgkin's Lymphoma
Conditions
Keywords
NHL, Non-Hodgkin's Lymphoma, T-cell Lymphoma
Brief summary
This is a Phase II, multicenter, single-arm, open-label study of oral lenalidomide monotherapy administered to subjects with relapsed or refractory T-cell lymphoma. This study will be conducted in two phases: a Treatment Phase and a Follow-up Phase. Subjects who qualify for enrollment into the study will enter the Treatment Phase and receive single-agent lenalidomide 25 mg once daily on Days 1-21 every 28 days (28-day cycles). Subjects may continue participation in the Treatment Phase of the study for a maximum duration of 24 months, or until disease progression or unacceptable adverse events develop. All subjects who discontinue the Treatment Phase for any reason will continue to be followed until progression of disease or until next lymphoma treatment is given, whichever comes first, during the Follow-up Phase. Objectives: Primary: • To determine the efficacy of lenalidomide monotherapy in relapsed or refractory T-cell Non-Hodgkin's Lymphoma (NHL). Efficacy will be assessed by measuring the response rate, tumor control rate, duration of response, time to progression and progression free survival. Secondary: • To evaluate the safety of lenalidomide monotherapy as treatment for subjects with relapsed or refractory T-cell NHL.
Detailed description
Study was terminated. Study data assessment revealed that study drug is active, but is not likely to be sufficiently active as a single agent in this population for registration purposes.
Interventions
DRUGLenalidomide
Lenalidomide capsules, 25 mg daily for 21 days in each 28 day cycle
Sponsors
Celgene
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must understand and voluntarily sign an informed consent form. * Must be ≥ 18 years of age at the time of signing the informed consent form. * Must be able to adhere to the study visit schedule and other protocol requirements. * Biopsy-proven T-cell Non-Hodgkin's Lymphoma, either: * Peripheral T-cell Lymphoma (PTCL) whatever the subtype, or * Cutaneous T-cell Lymphoma (CTCL), but only the subtype mycosis fungoides. * Relapsed or refractory to previous therapy for T-cell Non-Hodgkin's Lymphoma. * Must have received at least one prior combination chemotherapy regimen. There is no limit on the number of prior therapies.
Exclusion criteria
* Cutaneous T-cell Lymphoma of subtype Sézary Syndrome.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants Categorized by Best Response as Determined by Investigator | Up to 24 months | Participant response assessed by investigator; criteria by B. Cheson in Journal of Clinical Oncology, 1999 (see article for more detail): * Complete Response(CR): Complete disappearance of all detectable disease * Complete Response Unconfirmed(CRu): CR, but indeterminate bone marrow * Partial Response(PR): \>50% decrease in six largest nodes/nodal masses * Stable Disease(SD): Less than PR, but not progressive disease * Relapsed Disease: In CR/CRu Patients, new lesions seen or increased by \>=50% in previous sites * Progressive Disease(PD): \>=50% increase from low in PR/Non-Responders |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Up to 24 months | Kaplan-Meier Estimate of duration of response calculated as the time from first computed tomography (CT) Scan or magnetic resonance imaging (MRI) that demonstrates at least a partial response to the first documentation of disease progression, including death due to Non-Hodgkin's Lymphoma. |
| Time-to-Progression | Up to 24 months | Kaplan-Meier estimate of time-to-progression is calculated as the time from the start of study drug therapy to the first documentation of progressive disease. |
| Progression-Free Survival | Up to 24 months | Kaplan-Meier estimate of progression-free survival is defined as the start of study drug therapy to the first observation of disease progression or death due to any cause. |
| Safety | Up to 24 months | Summary of Treatment-Emergent Events in Safety Population (participants with at least one dose of study drug). Events assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 3: Following is the scale: Grade 1=Mild Adverse Event (AE), Grade 2=Moderate AE, Grade 3=Severe and Undesirable AE, Grade 4=Life-threatening or Disabling AE, and Grade 5=Death Related to AE.) |
Countries
Australia, Belgium, France, United States
Participant flow
Recruitment details
Recruiting began March 2008; first participant enrolled 16 June 2008 and last participant enrolled 29 January 2010.
Pre-assignment details
Participants with relapsed or refractory, biopsy-proven, T-cell Non-Hodgkin's Lymphoma. Must have received at least one prior chemotherapy regimen which contained two cytotoxic agents.
Participants by arm
| Arm | Count |
|---|---|
| Single Agent Lenalidomide Oral lenalidomide 25 mg daily for 21 days every 28 days as tolerated for up to 24 months, until disease progression, or an unacceptable adverse event occurs. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Death | 5 |
| Overall Study | Disease Progression | 27 |
| Overall Study | New Lymphoma Treatment Started | 4 |
| Overall Study | Other | 1 |
| Overall Study | Study Terminated | 9 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Single Agent Lenalidomide |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 11.25 |
| Age, Customized <=18 years | 0 participants |
| Age, Customized >18 years and < = 65 years | 28 participants |
| Age, Customized >65 years | 26 participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Anaplastic large cell lymphoma, primary cutaneous | 1 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Anaplastic large cell lymphoma, primary systemic | 3 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Angioimmunoblastic T-cell lymphoma | 26 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Cutaneous T-cell lymphoma, mycosis fungoides var. | 3 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Extranodal NK T-cell lymphoma, nasal type | 1 Participants |
| Non-Hodgkin's Lymphoma Diagnosis/Histopathology Peripheral T-cell lymphoma, not otherwise charac | 20 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 3 participants |
| Race/Ethnicity, Customized Black | 4 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Race/Ethnicity, Customized Missing | 0 participants |
| Race/Ethnicity, Customized Other | 1 participants |
| Race/Ethnicity, Customized White | 45 participants |
| Region of Enrollment Australia | 8 participants |
| Region of Enrollment Belgium | 3 participants |
| Region of Enrollment France | 40 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / 54 |
| serious Total, serious adverse events | 29 / 54 |
Outcome results
Primary
Participants Categorized by Best Response as Determined by Investigator
Participant response assessed by investigator; criteria by B. Cheson in Journal of Clinical Oncology, 1999 (see article for more detail): * Complete Response(CR): Complete disappearance of all detectable disease * Complete Response Unconfirmed(CRu): CR, but indeterminate bone marrow * Partial Response(PR): \>50% decrease in six largest nodes/nodal masses * Stable Disease(SD): Less than PR, but not progressive disease * Relapsed Disease: In CR/CRu Patients, new lesions seen or increased by \>=50% in previous sites * Progressive Disease(PD): \>=50% increase from low in PR/Non-Responders
Time frame: Up to 24 months
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Complete Response (CR) | 4 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Complete Response Unconfirmed (CRu) | 2 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Partial Response (PR) | 6 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Stable Disease (SD) | 16 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Progressive Disease (PD) | 16 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | No Response Assessment | 9 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Other | 1 Participants |
| Single Agent Lenalidomide | Participants Categorized by Best Response as Determined by Investigator | Tumor Control (CR+CRu+PR+SD) | 28 Participants |
Secondary
Duration of Response
Kaplan-Meier Estimate of duration of response calculated as the time from first computed tomography (CT) Scan or magnetic resonance imaging (MRI) that demonstrates at least a partial response to the first documentation of disease progression, including death due to Non-Hodgkin's Lymphoma.
Time frame: Up to 24 months
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Agent Lenalidomide | Duration of Response | 3.55 Months |
Secondary
Progression-Free Survival
Kaplan-Meier estimate of progression-free survival is defined as the start of study drug therapy to the first observation of disease progression or death due to any cause.
Time frame: Up to 24 months
Population: Intent-to-treat (ITT) Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Agent Lenalidomide | Progression-Free Survival | 2.53 Months |
Secondary
Safety
Summary of Treatment-Emergent Events in Safety Population (participants with at least one dose of study drug). Events assessed using National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE, Version 3: Following is the scale: Grade 1=Mild Adverse Event (AE), Grade 2=Moderate AE, Grade 3=Severe and Undesirable AE, Grade 4=Life-threatening or Disabling AE, and Grade 5=Death Related to AE.)
Time frame: Up to 24 months
Population: Safety Population (received at least one dose of study drug)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single Agent Lenalidomide | Safety | At least 1 adverse event (AE) | 53 Participants |
| Single Agent Lenalidomide | Safety | At least 1 AE related to drug | 40 Participants |
| Single Agent Lenalidomide | Safety | At least 1 NCI CTCAE Grade 3-4 AE | 34 Participants |
| Single Agent Lenalidomide | Safety | At least 1 NCI CTCAE Gr 3-4 AE related to drug | 19 Participants |
| Single Agent Lenalidomide | Safety | At least 1 serious adverse event (SAE) | 29 Participants |
| Single Agent Lenalidomide | Safety | At least 1 SAE related to drug | 16 Participants |
| Single Agent Lenalidomide | Safety | At least 1 AE leading to drug withdrawal (WD) | 21 Participants |
| Single Agent Lenalidomide | Safety | At least 1 AE leading to drug interruption/WD | 19 Participants |
Secondary
Time-to-Progression
Kaplan-Meier estimate of time-to-progression is calculated as the time from the start of study drug therapy to the first documentation of progressive disease.
Time frame: Up to 24 months
Population: Due to early termination of study, data not analyzed. See outcome #4 for progression-free survival.