Acute Myeloid Leukemia
Conditions
Brief summary
Double-Blind Placebo-Controlled Randomized Phase 2 Study evaluating the efficacy of lirilumab (IPH2102/BMS-986015) as Maintenance Treatment administered in elderly patients with Acute Myeloid Leukemia (AML) in first complete remission
Interventions
DRUGIPH2102 at 0.1 mg/kg
every 3 months
DRUGIPH2102 at 1 mg/kg
every 4 weeks
every 4 weeks
Sponsors
Innate Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Primary or secondary Acute Myeloid Leukemia (AML, defined according to WHO 2008 criteria), in first CR/CRi (according to the revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia J Clin Oncol. 2003 Dec 15; 21(24):4642-9 see appendix 19.3) following induction chemotherapy and who received 1 or 2 consolidation cycles. Induction chemotherapy should be performed within 6 months before randomization. Consolidation cycle is defined as any chemotherapy administered within 3 months following CR and including aracytine irrespective of the administered dose(s). A minimum of one and maximum of 2 cycles should be administered before enrollment 2. Patients not eligible for an allogeneic hematopoietic cell transplantation 3. Age 60 to 80 4. ECOG Performance status of 0 or 1 5. Clinical laboratory values at screening * Calculated creatinine clearance (according to MDRD) \> 60 ml/min/1.73 m2 * Platelet \> 75 x 109/l * Hemoglobin ≥ 10 g/dl supported or unsupported by transfusions * ANC \> 1 x 109/l * Total Bilirubin levels ≤ 1.5 ULN * ALT and AST ≤ 3 ULN 6. Recovery from acute toxicity of previous anti-tumor therapy 7. Male patients who accept and are able to use contraception methods recognized as highly effective. 8. Signed informed consent prior to any protocol specific procedure.
Exclusion criteria
1. Acute Promyelocytic Leukemia with t (15; 17), or its molecular equivalents (PML-RARA) 2. Favorable risk AML corresponding defined as t(8;21) or inv (16) and t(16;16) and their molecular equivalents (AML-ETO and CBFB-MYH11) 3. Last consolidation completed more than 3 months prior to first dosing 4. Concomitant treatment by chemotherapy, immunotherapy or by systemic corticosteroids 5. Within 28 days prior to first dosing: chemotherapy or systemic corticosteroid treatment 6. History of allogeneic hematopoietic cell transplantation or solid organ transplantation 7. History of high dose chemotherapy with autologous hematopoietic transplantation performed as treatment for AML 8. Use of any investigational agent within 2 months prior to the first dosing 9. Use of growth factors (G- or GM-CSF or EPO) within 28 days prior to first dosing 10. Any irradiation within the last 3 months except for analgesic intent 11. Intermittent or continuous renal replacement therapy 12. Abnormal cardiac status with any of the following * Ejection fraction (measured by ultra-sound or radionuclide imaging) \<50% * Myocardial infarction within the previous 6 months * QTc ≥ 480 ms (Bazett's). 13. Current active infectious disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen and/or negative anti Hbs Antibody 14. Auto-immune disease: * Which currently or previously required systemic immunosuppressive or immuno-modulatory therapy (including corticosteroids administered by systemic route) * And/or has substantial probability to cause an irreversible injury to any tissue * And/or is recent or unstable or has substantial risk to progress and cause severe complications. 15. Serious concurrent uncontrolled medical disorder 16. History of another malignancy (apart from myelodysplastic syndromes, basal cell carcinoma of the skin, or in situ cervix carcinoma) except if free of disease for ≥ 3 years 17. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Leukemia-Free Survival | from date of randomization until the date of first documented relapse, assessed up to 48 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | from the time of patient signing the consent form until 28 days after the last administration, or until the patient's last study visit, up to 24 months | Number of Participants with Adverse Events based on full physical examination each treatment visit and collection of AEs |
Countries
France
Participant flow
Recruitment details
169 patients were screened and 152 patients were randomized and treated in France
Participants by arm
| Arm | Count |
|---|---|
| IPH2102 at 1 mg/kg lirilumab (IPH2102/BMS986015) at 1 mg/kg
IPH2102 at 1 mg/kg: every 4 weeks | 51 |
| IPH2102 at 0.1 mg/kg lirilumab (IPH2102/BMS986015) at 0.1 mg/kg
IPH2102 at 0.1 mg/kg: every 3 months
Placebo (normal saline solution): every 4 weeks | 50 |
| Placebo (Normal Saline Solution) Normal saline solution
Placebo (normal saline solution): every 4 weeks | 51 |
| Total | 152 |
Baseline characteristics
| Characteristic | IPH2102 at 0.1 mg/kg | Placebo (Normal Saline Solution) | Total | IPH2102 at 1 mg/kg |
|---|---|---|---|---|
| Age, Continuous | 70 years | 68 years | 70 years | 70 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment France | 50 participants | 51 participants | 152 participants | 51 participants |
| Sex: Female, Male Female | 16 Participants | 17 Participants | 61 Participants | 28 Participants |
| Sex: Female, Male Male | 34 Participants | 34 Participants | 91 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 32 / 51 | 26 / 50 | 23 / 51 |
| other Total, other adverse events | 38 / 51 | 48 / 50 | 43 / 51 |
| serious Total, serious adverse events | 12 / 51 | 17 / 50 | 11 / 51 |
Outcome results
Primary
Leukemia-Free Survival
Time frame: from date of randomization until the date of first documented relapse, assessed up to 48 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IPH2102 at 1 mg/kg | Leukemia-Free Survival | 6.7 MONTHS |
| IPH2102 at 0.1 mg/kg | Leukemia-Free Survival | 17.6 MONTHS |
| Placebo (Normal Saline Solution) | Leukemia-Free Survival | 13.9 MONTHS |
Secondary
Number of Participants With Adverse Events
Number of Participants with Adverse Events based on full physical examination each treatment visit and collection of AEs
Time frame: from the time of patient signing the consent form until 28 days after the last administration, or until the patient's last study visit, up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IPH2102 at 1 mg/kg | Number of Participants With Adverse Events | 43 Participants |
| IPH2102 at 0.1 mg/kg | Number of Participants With Adverse Events | 49 Participants |
| Placebo (Normal Saline Solution) | Number of Participants With Adverse Events | 47 Participants |