Acute Myeloid LeukemiaPhase 2AARONNCT04913922
Relatlimab With Nivolumab and 5-Azacytidine for the Treatment of AML
A Phase 2 study testing Azacitidine Injection, Nivolumab and Relatlimab in people with Acute Myeloid Leukemia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
Trial summary
The clinical trial will test the safety and tolerability of a combination therapy (azacitidine in combination with two checkpoint inhibitors, nivolumab [Anti-PD1] and relatlimab [Anti-LAG3]) in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and patients ≥ 65 years with initial diagnosis of AML. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Azacitidine Injection, Nivolumab and Relatlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 5 May 2021to Mar 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Hospital, LMU Munich
Munich, 81377
Marion Subklewe, MD, +49-894400-0, marion.subklewe@med.uni-muenchen.de
Veit Bücklein, MD, +49-89-4400-0, veit.buecklein@med.uni-muenchen.de
About this study
Official title: 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
The clinical trial will test the safety and tolerability of a combination therapy (azacitidine in combination with two checkpoint inhibitors, nivolumab [Anti-PD1] and relatlimab [Anti-LAG3]) in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and patients ≥ 65 years with initial diagnosis of AML.
Primary objectives are:
- maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the combination therapy during the lead-in phase of the clinical trial (6-12 patients) and
- objective response rate (ORR) of the combination therapy in the phase II part of the study (up to 24 patients).
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Azacitidine Injection, Nivolumab, Relatlimab
- Keywords
- AML, relapsed, refractory, checkpoint blockade, immune checkpoint inhibition
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azacitidine InjectionDrug
s.c. 75 mg/m2 BSA for 7 days
NivolumabDrug
480 mg i.v.
RelatlimabDrug
80-160mg i.v.
| Study group | Role | What they receive |
|---|---|---|
| Combination therapy | Experimental | 5-azacitidine 75 mg/m2 body surface area s.c. for 7 days nivolumab 480mg i.v. day 1 relatlimab 80-160mg i.v. day 1
repeat day 28 Receives: Drug: Azacitidine Injection; Drug: Nivolumab; Drug: Relatlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
To determine the MTD of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML.
Measured: after completion of the first cycle in the fist 6-12 patients, approximately during the first 6-12 months of study conduct
Dose-limiting toxicities (DLTs)
To determine the DLT of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML.
Measured: after completion of the first cycle in the fist 6-12 patients, approximately during the first 6-12 months of study conduct
Objective response rate (ORR)
To estimate the ORR to treatment with relatlimab + nivolumab + 5-azacytidine in patients with R/R AML and Patients ≥65 years with initial diagnosis of AML
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Secondary outcomes (5)
Hematologic improvement
To determine the number of patients with R/R AML or Patients ≥65 years with initial diagnosis of AML treated with relatlimab + nivolumab + 5-azacytidine who have a hematologic improvement (HI) in platelets, hemoglobin, or absolute neutrophil count (ANC)
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Blast reduction
To determine the number of patients with R/R AML or Patients ≥65 years with initial diagnosis of AML treated with relatlimab + nivolumab + 5-azacytidine who have a blast reduction (defined as ≥50% reduction in blast percentage compared to baseline blast percentage in bone marrow)
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Duration of response (DOR)
To assess the duration of response (DOR) of patients with R/R AML or Patients ≥65 years with initial diagnosis of AML treated with relatlimab + nivolumab + 5-azacytidine.
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Disease-free survival (DFS)
To assess the disease-free survival (DFS) of patients with R/R AML or Patients ≥65 years with initial diagnosis of AML treated with relatlimab + nivolumab + 5-azacytidine.
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Overall survival (OS)
To assess the overall survival (OS) of patients with R/R AML or Patients ≥65 years with initial diagnosis of AML treated with relatlimab + nivolumab + 5-azacytidine.
Measured: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2021
- Study start5 May 2021
- Primary completionMar 2025 (estimated)
- Study completionMar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ludwig-Maximilians - University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Veit Bücklein, MD, Ludwig-Maximilians - University of Munich
- Investigators
- Marion Subklewe, MD, Principal investigator, Department of Medicine III, University of Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04913922
- Sponsor's protocol ID
- CA224-065
- Acronym
- AARON
- Status last verified
- Nov 2022
- First submitted
- 14 May 2021
- Last updated
- 8 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04913922
- Acronym / sponsor ID
- AARON / CA224-065
- Conditions
- Acute Myeloid Leukemia
- Keywords
- AML, relapsed, refractory, checkpoint blockade, immune checkpoint inhibition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ludwig-Maximilians - University of MunichUniversity, hospital or other
- Study start
- 5 May 2021 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Mar 2026 (estimated)
- First posted
- 4 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The clinical trial will test the safety and tolerability of a combination therapy (azacitidine in combination with two checkpoint inhibitors, nivolumab [Anti-PD1] and relatlimab [Anti-LAG3]) in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and patients ≥ 65 years with initial diagnosis of AML.
Primary objectives are:
- maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of the combination therapy during the lead-in phase of the clinical trial (6-12 patients) and
- objective response rate (ORR) of the combination therapy in the phase II part of the study (up to 24 patients).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination therapy | Experimental | Drug: Azacitidine Injection, Drug: Nivolumab, Drug: Relatlimab5-azacitidine 75 mg/m2 body surface area s.c. for 7 days nivolumab 480mg i.v. day 1 relatlimab 80-160mg i.v. day 1 repeat day 28 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
- Patients aged ≥65 years with previously untreated AML who are unfit for or decline standard induction therapy.
- Patients not eligible for intensive induction chemotherapy and/or allogeneic stem cell transplant.
- Age ≥18 years
- ECOG Performance Status ≤2
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azacitidine Injections.c. 75 mg/m2 BSA for 7 days | Drug | Combination therapy |
| Nivolumab480 mg i.v. | Drug | Combination therapy |
| Relatlimab80-160mg i.v. | Drug | Combination therapy |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: after completion of the first cycle in the fist 6-12 patients, approximately during the first 6-12 months of study conduct
To determine the MTD of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML.
Dose-limiting toxicities (DLTs)
Time frame: after completion of the first cycle in the fist 6-12 patients, approximately during the first 6-12 months of study conduct
To determine the DLT of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML.
Objective response rate (ORR)
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
To estimate the ORR to treatment with relatlimab + nivolumab + 5-azacytidine in patients with R/R AML and Patients ≥65 years with initial diagnosis of AML
5 secondary outcomes
Hematologic improvement
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Blast reduction
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Duration of response (DOR)
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Disease-free survival (DFS)
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Overall survival (OS)
Time frame: During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marion Subklewe, MD principal investigator
Department of Medicine III, University of Munich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Azacitidine Injection, Nivolumab and Relatlimab in people with Acute Myeloid Leukemia, run by Ludwig-Maximilians - University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marion Subklewe, MD (+498944000, marion.subklewe@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: after completion of the first cycle in the fist 6-12 patients, approximately during the first 6-12 months of study conduct). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.