None listed
Conditions
Brief summary
This study will investigate the safety and tolerabilty of escalating doses of oral azacitadine in combination with a fixed dose of lenalidominde and dexamethasone in patients with relapased/refractory multiple myeloma. This study is for patients who have previously been diagnosed with multiple myeloma and who have previously been treated unsuccessfully with lenalidomide. The dose levels of oral azacitadine are: 1 (A) 100mg for days 1-14 of 28 day cycle 2 (B) 100mg for days 1-21 of 28 day cycle 3 (C) 150mg for days 1-14 of 28 day cycle 4 (D) 150mg for days 1-21 of 28 day cycle 5 (E) 200mg for days 1-14 of 28 day cycle 6 (F) 200mg for days 1-21 of 28 day cycle The fixed dose of lenalidomide is 25mg on Day 1 to 21 of each 28-day cycle. The fixed dose of dexamethasone is 40mg on Day 1, 8, 15 and 22 or each 28-day cycle. A total of up to 30 patients may take part in this trial. The first 3 patients will be enrolled in the lowest dose level 1(A). If this dose level is tolerated well by these patients, the next 3 patients will be enrolled in the next dose level 2(B), and so on until a dose level is reached where too many side effects are experienced. The dose level below the one with too many side effects will be declared the Maximum Tolerated Dose (MTD) and patients will drop back to this dose level and continue at this dose. This MTD dose level will be expanded to allow up to 22 patients to receive this dose. You may be eligible to join this study is you are above 18 years of age and have adequate liver, kidney and bone marrow function; have no contrainidications to the use of azacitidine, lenalidomide or dexamethasone; you provide consent; you have not had therapy for your multiple myeloma in the last 4 weeks and agree to practise abstinence or use contraception for the specified time period.
Interventions
Oral azacitadine will be administered at escalating dosing schedules in the dose escalation phase:
1 (A) 100mg for days 1-14 of 28 day cycle
2 (B) 100mg for days 1-21 of 28 day cycle
3 (C) 150mg for days 1-14 of 28 day cycle
4 (D) 150mg for days 1-21 of 28 day cycle
5 (E) 200mg for days 1-14 of 28 day cycle
6 (F) 200mg for days 1-21 of 28 day cycle
Oral azacitidine will be administered in conjunction with 25mg oral lenalidomide on day 1-21 for each 28-day cycle and 40mg oral dexamethasone at Da
Oral azacitadine will be administered at escalating dosing schedules in the dose escalation phase: 1 (A) 100mg for days 1-14 of 28 day cycle 2 (B) 100mg for days 1-21 of 28 day cycle 3 (C) 150mg for days 1-14 of 28 day cycle 4 (D) 150mg for days 1-21 of 28 day cycle 5 (E) 200mg for days 1-14 of 28 day cycle 6 (F) 200mg for days 1-21 of 28 day cycle Oral azacitidine will be administered in conjunction with 25mg oral lenalidomide on day 1-21 for each 28-day cycle and 40mg oral dexamethasone at Day 1, 8, 15, 22 of each 28-day cycle. At least three patients per dosing schedule will be treated. The first patients will start at the lowest dose level and be assessed for their tolerabilty of the combination of drugs at the end of cycle one. If there are no dose limiting toxicites observed, the following three patients will be commenced on the next dose level. This will continue until a dose level is reached in which patients begin to experience toxicities. The dose level below that level will be deemed the Maximum Tolerated Dose (MTD) . In the Dose Expansion phase all future patients, and up to 20, will be treated at the MTD.
Sponsors
The Alfred Hospital
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years and above 2. Confirmed diagnosis of MM as per IMWG criteria 3. ECOG performance status 0-2 4. Relapsed and/or refractory MM with a history of lenalidomide failure where lenalidomide failure is defined as a) Progressive disease while on a lenalidomide containing regimen OR b) Progressive disease within 60 days of completing a lenalidomide containing regimen OR c)Failure to achieve at least a minimal response (MR) with 4 cycles of lenalidomide containing therapy when such therapy was administered either as part of initial therapy for newly diagnosed MM or as salvage therapy for the treatment of relapsed/refractory MM. 5. Adequate liver and kidney function (<2 x institutional upper limit of normal) 6. Platelet count > 75 x 109/L, absolute neutrophil count > 1.0 x 109/L 7. No contraindication to the use of azacitidine, lenalidomide or dexamethasone 8. Patient has voluntarily agreed and has given written informed consent. 9. Life expectancy of > 8 weeks 10. Patient must be >4 weeks from prior chemotherapy, radiotherapy, biological therapy, immunotherapy, major surgery or any other investigational anti-cancer therapy prior to the first dose of study drug 11. All females of childbearing potential (FOCBP)** must agree to have two negative pregnancy tests in the 24hrs before commencing lenalidomide and use two reliable methods of contraception simultaneously or to practice complete abstinence from any sexual contact during the following time periods related to this study: 1) for at least 28 days before starting study; 2) while participating in the study; 3) dose interruptions; and 4) for at least 28 days after study treatment discontinuation. The two methods of reliable contraception must include one highly effective method and one additional effective method to prevent pregnancy, not plan on conceiving children during or within 6 months following lenalidomide 12. All male participants must practice complete abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 28 days following study drug discontinuation, even if he has undergone a successful vasectomy. ** A female of childbearing potential is defined as a sexually mature woman who: 1 has not undergone a hysterectomy or bilateral oophorectomy or 2, has not been naturally post-menopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (I.e, has had menses at any time in the preceding 24 consecutive months).
Exclusion criteria
1. Patients with monoclonal gammopathy of uncertain significance. 2. Primary amyloidosis 3. Patients who have received prior allogeneic transplantation < 12 months prior to entering study 4. Patients who have had prior allogeneic transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements 6. Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcimnoma or in situ cancer of the cervix). 7. Pregnant or lactating women. 8. Known hepatitis B, Hepatitis C, HIV infection, other immunosuppressive therapy or autoimmune disease
Outcome results
None listed