Oral Azacitidine, Lenalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Phase 1

• Conditions: Multiple Myeloma; Cancer - Myeloma

• Registration Number: ACTRN12613000283774
• Lead Sponsor: The Alfred Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-03-08
• Study Completion: 2018-01-24
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To examine the safety and tolerability, and determine the maximum tolerated dose of azacitidine when administered orally in combination with fixed dose lenalidomide and dexamethasone in patients with relapsed/refractory myeloma who have a history of lenalidomide failure. [During the trial treatment at the completion of each dose level]