Myelodysplastic Syndrome
Conditions
Keywords
IPSS Int-2, high risk myelodysplastic syndrome, MDS), 5q31.1 deletions
Brief summary
This is a phase II study of lenalidomide in patients with myelodysplastic syndrome (MDS) and with acute myeloid leukemia (AML) with trilineage dysplasia. Patients will receive two cycles of lenalidomide. Patients who respond may given additional cycles of lenalidomide until disease progression.
Detailed description
This is a single center open label phase II study of lenalidomide in IPSS Int-1 with increased blasts or hematologic needs with 5q31.1 deletions who have failed to respond to standard dose lenalidomide., IPSS Int-1 with increased blasts or hematologic needs without 5q31.1 deletions, and Int-2 and high risk myelodysplastic syndrome (MDS) patients with or without 5q31.1 deletions, regardless of whether they have received lenalidomide previously or not. Patients will receive two cycles of 15 mg daily lenalidomide (later amended to 50 mg daily lenalidomide) given on days 1-28 out of a 42 day cycle. Within each of the two cycles of lenalidomide, patients will be given up to three weeks with no drug treatment to recover. Patients who fail to respond after two cycles of treatment may receive two additional cycles if stable. Patients who develop clinical response may continue to receive drug until disease progression.
Interventions
DRUGLenalidomide 50 mg
DRUGLenalidomide 15 mg
Sponsors
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years at the time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements. * MDS or MDS/AML * Patients must not have received any other treatment for their disease, including hematopoietic growth factors, within three weeks of beginning the trial * ECOG performance status of 0, 1, or 2 at study entry * All study participants must be registered into the mandatory REMS® program, and be willing and able to comply with the requirements of RevAssist®. * Patients must have no clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia. * Subjects must agree to use appropriate contraception.
Exclusion criteria
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide). * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Use of any other experimental drug or therapy within 21 days of baseline. * Known hypersensitivity to thalidomide. * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Any prior use of lenalidomide except for MDS patients with del 5q31.1 abnormalities.. * Concurrent use of other anti-cancer agents or treatments. * Patients may not have received prior AML induction chemotherapy or stem cell transplant. However, patients with secondary MDS who have received a stem cell transplant for other indications (eg lymphoma, multiple myeloma) will be eligible.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 15 weeks | Number of participants with a complete or partial response according to International Working Group 2006 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3-4 Toxicity | Up to 8 months | Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide. |
Countries
United States
Participant flow
Pre-assignment details
2 participants on the 15mg arm and 3 participants on the 50mg arm were screen failures.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide 15 mg Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 15 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression.
Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described.
Patients without evidence of response after 4 cycles will be taken off-study. | 9 |
| Lenalidomide 50 mg Patients diagnosed with high risk Myelodysplastic syndrome (MDS), regardless of 5q deletion status, will receive lenalidomide 50 mg per day orally, on days 1-28 of a 42 day cycle for 2 cycles. At this point, patients meeting protocol specified response criteria will proceed to Continuing Therapy on a reduced dose of lenalidomide until progression.
Patients not achieving response will receive 2 additional cycles of treatment, whereupon response will again be assessed. Patients achieving response at this point will proceed to Continuing Therapy as described.
Patients without evidence of response after 4 cycles will be taken off-study. | 18 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 6 | 12 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Lenalidomide 15 mg | Lenalidomide 50 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 14 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Continuous | 77 years | 70 years | 72 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 9 | 2 / 18 |
| other Total, other adverse events | 7 / 9 | 13 / 18 |
| serious Total, serious adverse events | 3 / 9 | 9 / 18 |
Outcome results
Primary
Response Rate
Number of participants with a complete or partial response according to International Working Group 2006 criteria.
Time frame: 15 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lenalidomide 15 mg | Response Rate | Complete response | 0 Participants |
| Lenalidomide 15 mg | Response Rate | Partial response | 0 Participants |
| Lenalidomide 50 mg | Response Rate | Complete response | 0 Participants |
| Lenalidomide 50 mg | Response Rate | Partial response | 2 Participants |
Secondary
Grade 3-4 Toxicity
Number of participants who experienced at least one grade 3-4 non-hematological toxicity by CTCAE 3.0 that was attributed to lenalidomide.
Time frame: Up to 8 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lenalidomide 15 mg | Grade 3-4 Toxicity | 6 Participants |
| Lenalidomide 50 mg | Grade 3-4 Toxicity | 12 Participants |