MDS
Conditions
Keywords
MDS, Low risk disease, IPSS
Brief summary
This phase II study will evaluate the safety and efficacy of combining two active agents;Revlimid® (lenalidomide) and low dose Vidaza® (azacitidine) for the treatment of patients with low to intermediate-1 MDS excluding patients with 5 q deletion. The rationale for adding Vidaza® (azacitidine) after 3 months of revlimid monotherapy is that combination therapy will result in higher response rates, and potentially longer response duration than that achieved with either agent. STUDY OBJECTIVES: Primary: To determine the safety and tolerability of the combination of Revlimid® (lenalidomide) and low dose Vidaza® (azacitidine) in patients with low - intermediate-1 risk MDS non 5 q deletion who have not responded after 3 months of Revlimid® (lenalidomide) monotherapy Secondary: To determine the response rate in patients with low - intermediate-1 risk MDS non 5 q deletion receiving Revlimid® (lenalidomide) in combination with low dose Vidaza® (azacitidine), as defined by the IWG 2006 Revised Response Criteria
Detailed description
Eligibility criteria 1. Understand and voluntarily sign an informed consent form. 2. Age 18 years at the time of signing the informed consent form. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Diagnosis of low- or intermediate-1-risk IPSS (see Appendix III) MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33. Pathologic diagnosis via pathology performed at Rush University Medical Center or made available to Rush from outside institution. 5. Prior treatment with \< 3 cycles (84 days) of Revlimid® (lenalidomide) are eligible for enrollment regardless of response. 6. ECOG performance status of 2 at study entry (see Appendix II). 7. Disease free of prior malignancies for \> 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma insitu of the cervix or breast. 8. Serum bilirubin levels \< 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. 9. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) levels \< 2 x ULN. 10. Serum creatinine levels \< 1.5 x ULN 11. Absolute neutrophil count \> 1000/mm³ 12. Platelet count \> 30,000/mm³ 13. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Interventions
DRUGLenalidomide and azacitidine combination
lenalidomide 10 mg will be administered orally on Days 1-28 of each 28-day cycle. Patients who fail to achieve an erythroid response per 2006 IWG criteria after 3 cycles of monotherapy will receive lenalidomide at the same dose administered in cycle 3 and low-dose azacitidine25 mg/m2 subcutaneously (SC) or intravenously (IV) for 5 days (on Days 1-5) of every 28-day cycle. Patients who fail to respond (2006 IWG criteria) after receiving two cycles of combination therapy will receive lenalidomide at the same dose administered in Cycle 3 and azacitidine 50 mg/m2 SC or IV given daily on Days 1-5 of each 28-day cycle, if no grade 4 toxicity developed or no delay greater than 2 weeks in starting a new cycle was experienced during the first 2 cycles of combination therapy.
Sponsors
Celgene Corporation
Rush University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
Patients with low to Int-1 risk MDS 1. ECOG performance status of \< 2 at study entry (see Appendix II). 2. Disease free of prior malignancies for 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma insitu of the cervix or breast. 3. Serum bilirubin levels \< 1.5 times the upper limit of the normal range for the laboratory (ULN). Higher levels are acceptable if these can be attributed to active hemolysis or ineffective erythropoiesis. 4. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) levels \< 2 x ULN. 5. Serum creatinine levels 1.5 x ULN 6. Absolute neutrophil count \> 1000/mm³ 7. Platelet count \> 30,000/mm³ 8. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. 9. Females of childbearing potential (FCBP)† must have a negative serum or urine
Exclusion criteria
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 2. Pregnant or breast feeding females. Lactating females must agree not to breast feed while taking Revlimid® (lenalidomide). 3. 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. 4. Use of any other experimental drug or therapy within 28 days of baseline. 5. Known hypersensitivity to lenalidomide, azacitidine, or mannitol. 6. Any prior use of Vidaza® (azacitidine). 7. Prior use of Revlimid® (lenalidomide) for more than 84 days (three 28 day cycles). 8. Concurrent use of other anti-cancer agents or treatments. 9. Known positive for HIV or infectious hepatitis, type B or C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Revlimid and Azacitidine Combination | Study was closed and outcome unable to be measured. | To determine the number of subjects who develop grade 4 toxicity while on combination therapy. |
Countries
United States
Participant flow
Recruitment details
Recruitment from approximately 2010-2012.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide and Azacitidine Combination Lenalidomide and azacitidine combination to be utilized in patients who did not respond to 3 months of lenalidomide monotherapy.
Lenalidomide and azacitidine combination: lenalidomide 10 mg will be administered orally on Days 1-28 of each 28-day cycle. Patients who fail to achieve an erythroid response per 2006 IWG criteria after 3 cycles of monotherapy will receive lenalidomide at the same dose administered in cycle 3 and low-dose azacitidine25 mg/m2 subcutaneously (SC) or intravenously (IV) for 5 days (on Days 1-5) of every 28-day cycle.
Patients who fail to respond (2006 IWG criteria) after receiving two cycles of combination therapy will receive lenalidomide at the same dose administered in Cycle 3 and azacitidine 50 mg/m2 SC or IV given daily on Days 1-5 of each 28-day cycle, if no grade 4 toxicity developed or no delay greater than 2 weeks in starting a new cycle was experienced during the first 2 cycles of combination therapy. | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | funding withdrawn | 1 |
Baseline characteristics
| Characteristic | Lenalidomide and Azacitidine Combination | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 2 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 2 Participants | — |
| Sex: Female, Male Female | 1 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Safety and Tolerability of Revlimid and Azacitidine Combination
To determine the number of subjects who develop grade 4 toxicity while on combination therapy.
Time frame: Study was closed and outcome unable to be measured.
Population: Study was unable to be completed since funding was withdrawn.