None listed
Conditions
Brief summary
This study will evaluate the safety and efficacy of Combining Oral Azacitidine and Dendritic Cell Vaccination Vididencel in maintenance for Acute Myeloid Leukemia. Who is it for? You may be eligible to join this study if you are aged 16 and above and have Acute Myeloid Leukemia in first complete remission following intensive chemotherapy, not planned for allogeneic stem cell transplant Study details: This study is part of the International AML Platform Consortium. Participants in this study will be randomly allocated (by chance) to one of two treatment groups. Participants in one group will receive the oral drug Azacitidine daily on Days 1-14 of each 28 day cycle and a course of vididencel will be administered intradermally on cycle 1 (Day 1, Day 15), Cycle 2 (Day 1, Day 15), Cycle 4 day 1, Cycle 5 day 1, and Cycle 6 day 1. Oral-Aza 300mg will continued until progression to >15% blasts or unacceptable adverse events. Participants in the other group will receive the oral drug Azacitidine daily on Days 1-14 of each 28 day cycle, continued until progression to >15% blasts or unacceptable adverse events. Patient with low blast count (5-15%) can have oral Aza dosing regimen increased to 21 days per cycle, if Investigators finds that beneficial for the patient. As part of the study, participants will have blood tests at the start of each cycle (every 28 days) and measurable residual disease testing on bone marrow samples at the end of each second cycle until cycle 6 and then end of every 3 cycles. We hope that the results from this trial will be used to help these new treatments which may be better for people with AML than what is currently available become accessible to the general population at faster than the normal process.
Interventions
This domain of the AMLM22 platform trial (ACTRN12619000248167) is a randomised, 2-arm trial that will investigate the efficacy of oral azacitidine combined with an allogeneic dendritic cell vaccine vididencel, compared with oral azacitidine alone, in maintaining or inducing negativity for measurable residual disease (MRD) in AML patients in first complete remission (CR1) following intensive chemotherapy, not planned for alloSCT.
Oral tablet -Aza 300mg is administered orally daily on days 1-14 o
This domain of the AMLM22 platform trial (ACTRN12619000248167) is a randomised, 2-arm trial that will investigate the efficacy of oral azacitidine combined with an allogeneic dendritic cell vaccine vididencel, compared with oral azacitidine alone, in maintaining or inducing negativity for measurable residual disease (MRD) in AML patients in first complete remission (CR1) following intensive chemotherapy, not planned for alloSCT. Oral tablet -Aza 300mg is administered orally daily on days 1-14 of repeated 28-day cycles, continued until progression to more than 15% blasts or unacceptable adverse events. Patients with low level AML relapse with 5-15% blasts in blood or bone marrow can have the dosing regimen increased to 21 days per cycle at the discretion of the treating investigator. Vididencel is administered as an intradermal vaccine. A primary course of vididencel will be administered intradermally by a trained clinician on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 2 Day 15 (totaling 4 injections) at a dose of 25 x 106 cells/vc, followed by a booster course of 3 additional injections on Day 1 of cycle 4, Day 1 of cycle 5 and Day 1 of cycle 6 at a dose of 10 x 106 cells/vc. The intervention will be administered as inpatient, and administration and visit details will be captured in a electronic database. Patient will receive 24 cycles of treatment but the vididencel will be only administered according to the previous paragraph. Disease progression with greater than or equal to 15% blasts in bone marrow and/or peripheral blood, Unacceptable toxicity or Adverse event are considered sufficient reasons for discontinuing a patient from the trial treatment. Trial has 2 stages: 1. Stage 1: Pilot Phase, n = 40 2. Stage 2: Proof of concept, n = 100 The two participant groups will have separate recruitment. The first (pilot) stage will consist of 40 patients. Patients will be randomized 1:1 in each age stratum until a total of 40 patients has been randomized. If there are no adverse safety signals the second (proof of concept) stage will open and an additional 100 patients will be randomized. Both stage patient will have the same the same dosing. A pause in recruitment after stage 1 completes enrolment may be required for Trial management committee's (TMC) decision making. TMC will review the safety data from stage 1 patients and decide on the continuation of the trial to stage 2.
Sponsors
Australian Leukaemia and Lymphoma Group (ALLG)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient will be eligible for trial participation to this domain if they additionally meet the following criteria: 1. Is within 180 days of first CR / CRh / CRi. 2. Has undergone induction therapy with intensive chemotherapy, with or without consolidation therapy. Prior gemtuzumab ozogamicin, CPX-351 (Vyxeos), midostaurin or venetoclax used within the context of intensive induction are permitted. 3. Is not planned for alloSCT. 4. Has adequate bone marrow function, based on - Platelets greater than or equal 50 x 109/L - Neutrophils greater than or equal 0.5 x 109/L 5. Has an ECOG performance status of 0-3. 6. Has adequate organ function, defined as - Serum bilirubin less than or equal to 1.5 times the upper limit of normal (ULN); - Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 times the ULN; - Serum creatinine less than or equal to 2.5 times the ULN; 7. Agrees to follow the recommended contraception procedures for this treatment arm from Study Day 1 to 180 days after the last dose of study drug 8. Is able to adhere to the trial visit schedule and other protocol requirements; 9. Is able to swallow study medication. 10. Understands and voluntarily signs the consent form prior to any study related assessments/procedures are conducted.
Exclusion criteria
A patient will not be eligible for trial participation to this domain if they meet any of the following exclusion criteria: 1. Presence of any exclusion criteria noted in the AMLM22 Master Protocol. 2. AML associated with inv(16), t(8;21), t(16;16) or molecular evidence of such translocations (ie. RUNX1::RUNX1T1, CBFB::MYH11) 3. There is an intent to undertake a stem cell transplant procedure in CR1. 4. Prior hypomethylating agents used in induction of AML. (Hypomethylating agents for a prior myelodysplastic syndrome (MDS) are permitted). 5. Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure; 6. Subject is HIV positive; 7. Evidence of other clinically significant, uncontrolled conditions(s) including, but not limited to a) Uncontrolled and/or active systemic infection (viral, bacterial or fungal) (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment) b) Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIg) may participate. 8. Requirement for ongoing systemic immunosuppressive therapy equivalent to an average dose of greater than or equal to 10 mg of prednisone / day to avoid impairing the immune response to study therapy. 9. Active autoimmune disease, except for well controlled diabetes 10. Major surgical procedure (including open biopsy) within 28 days prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment. 11. Known or suspected hypersensitivity to azacitidine and/or vididencel (or its excipients) 12. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study; 13. Pregnant or lactating women 14. Any condition that would impair absorption of the study medication (i.e. short gut, malabsorption syndrome).
Outcome results
None listed