Combining three therapies for treating relapsed or refractory Acute Myeloid Leukemia
An Open-Label Phase II Study of Relatlimab (BMS-986016) With Nivolumab (BMS-936558) in Combination With 5-Azacytidine for the Treatment of Patients With Refractory/Relapsed Acute Myeloid Leukemia and Newly Diagnosed Older Acute Myeloid Leukemia Patients
This study is testing a new combination of three therapies to see if it can help patients with relapsed or refractory Acute Myeloid Leukemia who have run out of treatment options.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ludwig-Maximilians - University of Munich Academic / other |
| Drugs / interventions | nivolumab, relatlimab, chemotherapy, prednisone |
| Locations | 1 site (Munich) |
| Trial ID | NCT04913922 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and tolerability of a combination therapy involving azacitidine, nivolumab, and relatlimab for patients with relapsed or refractory Acute Myeloid Leukemia (AML). The study consists of two cohorts: one for patients who have failed prior chemotherapy and another for older patients who are unfit for standard treatment. The primary objectives include determining the maximum tolerated dose and assessing the objective response rate of the therapy. The trial aims to provide a new treatment option for patients who have limited alternatives.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory AML or those aged 65 and older with untreated AML who are unfit for standard induction therapy.
Not a fit: Patients who are eligible for intensive induction chemotherapy or allogeneic stem cell transplant may not benefit from this study.
Why it matters
Potential benefit: If successful, this combination therapy could offer a new treatment avenue for patients with difficult-to-treat AML.
How similar studies have performed: Other studies have explored similar combinations of checkpoint inhibitors and azacitidine, showing promising results in various hematological malignancies.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: Cohort 1 (R/R AML): - Patients with AML who have failed first line induction chemotherapy (consisting of a minimum of two intensive chemotherapy cycles, e.g. 7+3 or HAM) or patients with AML who have relapsed after achieving complete remission (CR), CRi, or CRp, or patients who have failed up to one prior salvage therapy Cohort 2 (frontline older AML): - Patients aged ≥65 years with previously untreated AML who are unfit for or decline standard induction therapy. General inclusion criteria: * Patients not eligible for intensive induction chemotherapy and/or allogeneic stem cell transplant. * Age ≥18 years * ECOG Performance Status ≤2 * Adequate organ function: Total bilirubin ≤2 x ULN (≤3 × ULN if due to leukemic involvement or Gilbert's syndrome) AST and ALT ≤2.5 × ULN (≤5.0 × ULN if due to leukemic involvement) Serum creatinine ≤2 × ULN or glomerular filtration rate (GFR) ≥50 mL/h * Adequate cardiac function: TTE with documented LVEF ≥50% * At least 2 weeks OR at least 5 half-lives interval from prior treatment to time of initiation of study medication * GvHD of grade ≤A on ≤10 mg prednisone without any additional immunosuppressive therapies (tacrolimus, ciclosporin, etc.) * Written informed consent * Negative pregnancy test and adequate methods of contraception for females of childbearing potential, adequate methods of contraception for males Exclusion Criteria: * Acute promyelocytic leukemia (APL) * Biphenotypic or bilineage leukemia * Known allergy or hypersensitivity to 5-azacytidine, nivolumab, relatlimab, or any of their components * History of life-threatening toxicity related to prior immune therapy * Previous treatment with immunotherapeutic drugs targeting PD-1/PD-L1 in combination with 5-azacytidine * Previous treatment with LAG-3 targeted agents * Known history of severe interstitial lung disease or severe pneumonitis * Known history (active, known, or suspected) of any of the following autoimmune diseases: inflammatory bowel disease rheumatoid arthritis systemic progressive sclerosis systemic lupus erythematosus autoimmune vasculitis * Active uncontrolled pneumonitis * Active uncontrolled infection * Symptomatic or poorly controlled CNS leukemia * Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent * Uncontrolled or significant cardiovascular disease * Troponin T (TnT) or I (TnI) \> 2 × institutional ULN * Organ allografts * Allogeneic hematopoietic stem cell transplantation within the last 100 days before first study drug administration * Active GvHD \> grade A * Known human immunodeficiency virus seropositivity * Known positivity for hepatitis B by surface antigen expression or active hepatitis C infection * Other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety * Patients unwilling or unable to comply with the protocol * Patients who are pregnant or breastfeeding * Prisoners and subjects who are compulsory detained
Where this trial is running
Munich
- University Hospital, LMU Munich — Munich, Germany (Recruiting)
Study contacts
- Principal investigator: Marion Subklewe, MD — Department of Medicine III, University of Munich
- Study coordinator: Marion Subklewe, MD
- Email: marion.subklewe@med.uni-muenchen.de
- Phone: +498944000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.