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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04913922

Studienbeginn:
Mai 2021

Letztes Update:
08.11.2022

Wirkstoff:
Azacitidine Injection, Nivolumab, Relatlimab

Indikation (Clinical Trials):
Leukemia, Leukemia, Myeloid, Leukemia, Myeloid, Acute

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Ludwig-Maximilians - University of Munich

Collaborator:
-

Studienleiter

Marion Subklewe, MD
Principal Investigator
Department of Medicine III, University of Munich

Kontakt

Marion Subklewe, MD
Kontakt:
Phone: +498944000
E-Mail: marion.subklewe@med.uni-muenchen.de» Kontaktdaten anzeigen

Veit Bücklein, MD
Kontakt:
Phone: +498944000
E-Mail: veit.buecklein@med.uni-muenchen.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital, LMU Munich
81377 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Marion Subklewe, MD
Phone: +49-894400-0
E-Mail: marion.subklewe@med.uni-muenchen.de

Veit Bücklein, MD
Phone: +49-89-4400-0
E-Mail: veit.buecklein@med.uni-muenchen.de» Ansprechpartner anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. 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.

2. 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.

3. 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

Secondary outcome:

1. Hematologic improvement (Time Frame - During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct):
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)

2. Blast reduction (Time Frame - During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct):
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)

3. 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):
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.

4. 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):
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.

5. Overall survival (OS) (Time Frame - During Phase II expansion phase, after completion of lead-in phase, approximately during months 7-48 of study conduct):
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.

Geprüfte Regime

Azacitidine Injection:
s.c. 75 mg/m2 BSA for 7 days
Nivolumab:
480 mg i.v.
Relatlimab:
80-160mg i.v.

Quelle: ClinicalTrials.gov

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