A Phase 2, Multi-center, open-label, randomized, parallel-group study of a lenalidomide (Revlimid) regimen or A sequential Azacitidine (Vidaza) plus Lenalidomide (Revlimid) regimen versus an Azacitidine (Vidaza) regimen for therapy of older subjects with newly diagnosed acute myeloid leukemia

Summary

This is a phase 2, multicenter, randomized, open-label, parallel-group study that will investigate the effect of a lenalidomide regimen or a sequential azacitidine plus lenalidomide regimen versus an azacitidine regimen for therapy of older subjects with newly diagnosed acute myeloid leukemia.

There will be 120 patients enrolled and randomized into three study arms:lenalidomide regimen, sequential azacitidine plus lenalidomide regimen or azacitidine regimen.

Lenalidomide regimen- on Day 1 of each 28-day .
treatment period patient will receive 50 mg/day for the first 2 cycles, 25 mg/day for the next 2 cycles and 10 mg/day continuously thereafter as long as their disease does not get worse

Azacitidine plus Lenalidomide regimen- Azacitdine will be administered 75 mg/m2/day on Days 1-7 of each 42-day cycle. On Day 7 the patient will receive a 21-day supply of lenalidomide to start the following day for Days 8-28 at a dosage of 50 mg/day followed by a 14-day break

Azacitidine (repeated cycles) at will be administered at 75 mg/m2/day on days 1-7 followed by a 21-day break.

The endpoint of the study are:

The primary endpoint of the study is one-year overall survival.

Secondary endpoints
 Overall remission rate (CR + CRi);
 Duration of remission (CR + CRi);
 Cytogenetic complete remission rate (CRc);
 Overall response rate (CR + CRi + PR);
 Progression-free survival (PFS);
 Event-free survival (EFS);
 Relapse-free survival (RFS);
 30-day mortality;
 Safety / tolerability (type, frequency, severity, and relationship of adverse events to
study treatments; physical examinations, vital signs; clinical laboratory evaluations,
and concomitant medications/procedures).

Exploratory endpoints
 Health-related quality-of-life utilizing the European Organization for Research and
Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30);
 Measures of healthcare resource utilization;
 Molecular and cellular features in the bone marrow or peripheral blood, potentially
including, but not limited to, cytogenetics, DNA/RNA methylation, gene variants
(single nucleotide polymorphism [SNP] and gene sequence), mRNA expression,
miRNA expression, and immunophenotyping of the presence, proportions and
activation status of immune cell populations

Participant Eligibility

1. Diagnosis of one of the following:
 Newly diagnosed, histologically confirmed de novo AML;
 AML with antecedent hematologic disorder (AHD) such as MDS not treated with
azacitidine, decitabine, cytarabine or lenalidomide;
 Therapy-related AML (following exposure to leukemogenic agents including
radiation, alkylating agents, topoisomerase II inhibitors) with the primary malignancy
in remission for at least 2 years;
2. Male or female subjects aged ≥ 65 at the time of signing the informed consent document;
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (see
Appendix B);
4. White blood cell (WBC) count ≤ 10 x 109/L at screening:
 Hydroxyurea is not allowed to attain this WBC count;
5. Adequate organ function, defined as:
 Serum bilirubin ≤ 2 times the upper limit of normal (ULN);
 Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3
times the ULN;
 Serum creatinine ≤ 2 times the ULN;
6. Females of childbearing potential (FCBP)1 must:
 Agree to use two reliable forms of contraception (see Appendix I) simultaneously or
to practice complete abstinence from heterosexual contact during the following time
periods related to this study: 1) for at least 28 days before starting lenalidomide; 2)
while participating in the study; 3) dose interruptions; and 4) for at least 28 days after
lenalidomide discontinuation (3 months after azacitidine discontinuation); and
 Have a negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) within 10 to
14 days prior to starting lenalidomide; and
 Have a negative serum or urine pregnancy test within 72 hours prior to starting study
prescribed therapy; and
 Have negative serum or urine pregnancy tests while on lenalidomide or during lenalidomide
dose interruptions, and after lenalidomide discontinuation, based on the frequency
outlined in Appendix I;
7. Female subjects must agree to abstain from breastfeeding during study participation and
for at least 28 days after lenalidomide discontinuation;
8. Male subjects (including those who have had a successful vasectomy) must:
 Practice complete abstinence or agree to the use of a physician-approved
contraceptive method during sexual contact with a pregnant female or a FCBP while
participating in the study, during dose interruptions and for at least 28 days after
lenalidomide discontinuation (3 months after azacitidine discontinuation); and
 Agree not to donate semen or sperm while taking lenalidomide and for 28 days after
lenalidomide discontinuation;
9. All subjects must:
 Understand that the IP(s) could have a potential teratogenic risk; and
 Agree to abstain from donating blood while taking lenalidomide and for 28 days after
lenalidomide discontinuation; and
 Agree not to share IP(s) with another person; and
 Be counseled about pregnancy precautions and risks of fetal exposure;
10. Understand and voluntarily sign an informed consent document prior to any study-related
assessments/procedures are conducted;
11. Able to adhere to the study visit schedule and other protocol requirements.