Relatlimab With Nivolumab and 5-Azacytidine for the Treatment of AML

NCT04913922 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CA224-065
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

AML; relapsed; refractory; checkpoint blockade; immune checkpoint inhibition

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD)

  To determine the MTD of relatlimab in combination with nivolumab and 5-azacytidine in patients with R/R AML.

  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.

  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

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

Secondary Outcomes (5)

• Hematologic improvement

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

• Blast reduction

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

• Duration of response (DOR)

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

• Disease-free survival (DFS)

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

• Overall survival (OS)

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

Other Outcomes (2)

• Immunological changes

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

• Molecular changes

  During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct

Study Arms (1)

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

Drug: Azacitidine Injection; Drug: Nivolumab; Drug: Relatlimab

Interventions

Azacitidine Injection DRUG

s.c. 75 mg/m2 BSA for 7 days

Combination therapy

Nivolumab DRUG

480 mg i.v.

Combination therapy

Relatlimab DRUG

80-160mg i.v.

Combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Study Sites (1)

University Hospital, LMU Munich

Munich, 81377, Germany

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Azacitidine; Nivolumab; relatlimab

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Marion Subklewe, MD

  Department of Medicine III, University of Munich

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marion Subklewe, MD

CONTACT

+498944000; marion.subklewe@med.uni-muenchen.de

Veit Bücklein, MD

CONTACT

+498944000; veit.buecklein@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 4, 2021
• Study Start: May 5, 2021
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2026
• Last Updated: November 8, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)