Azacitidine in Combination With Low Dose Intensity Venetoclax in Patients With AML Incl. Explorative AML Profiling

NCT05431257 | Recruiting Phase 2

• 1 other identifier: H-21030117
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief Summary

Multi-center phase II study of standard azacytidine treatment (AZA; D1-D7, 75mg/m2 qd) in combination with a short duration of "low-dose" venetoclax treatment (LD-VEN; D1-D14 before CR and D1-D7 after CR, 400mg qd) per 28 days cycle for elderly/unfit (arm 1) and relapsed/refractory (arm 2) patients with acute myeloid leukemia. AZA and LD-VEN treatment is combined with exploratory AML profiling using established platforms for OMICs analyses and ex vivo drug sensitivity and resistance testing. This will validate the feasibility of AML profiling in a clinical setting to predict responders and non-responders to AZA/LD-VEN therapy. The exploratory AML profiling program will also identify biomarkers as well as novel drugs and drug combinations applicable for treatment of AML patients in future clinical trial initiatives.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Overall response rate

  ORR(%) = CR rate(%)+CRi rate(%)+MLFS(%)

  1-1,5 year

• Composite complete remission rate

  Composite CR rate (%) = CR rate (%) + CRh rate (%)

  1-1,5 year

• Partial remission rate

  PR rate (%)

  1-1,5 year

Secondary Outcomes (8)

• Overall survival

  3,5-5 years

• Duration of response

  3,5-5 years

• Event free survival

  3,5-5 years

• Frequency and severity of adverse events

  3-3,5 years

• The correlation of ex vivo drug sensitivity with specific clinical responses

  1,5-2 years

Study Arms (1)

Elderly/unfit AML patients or sec. and R/R AML patients

EXPERIMENTAL

Drug: Venetoclax

Interventions

Venetoclax DRUG

Standard azacytidine treatment (AZA; D1-D7, 75mg/m2 qd) in combination with a short duration of "low-dose" venetoclax treatment (LD-VEN; D1-D14 before CR and D1-D7 after CR, 400mg qd) per 28 days cycle for elderly/unfit (arm 1) and relapsed/refractory (arm 2) patients with acute myeloid leukemia.

Elderly/unfit AML patients or sec. and R/R AML patients

Eligibility Criteria

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

You may qualify if:

• Written informed consent.
• Patients who present with one of the following (except acute promyelocytic leukemia).
• De novo or secondary AML unfit for standard induction therapy
• Relapsed/refractory AML after at least 1 line of prior therapies
• Written informed consent to participate in an exploratory research protocol including bio-banking, comprehensive AML profiling (genomics, transcriptomics, proteomics, etc.) and ex vivo drug sensitivity testing to assess venetoclax and other drug sensitivities.
• a) All patients are treated with azacitidine+venetoclax irrespective of the ex vivo screening results.
• ECOG Performance status ≤ 2 for patients ≥ 75 years of age OR ≤ 3 for patients ≥ 18 to 74 years of age.
• Leukocyte count \< 25 x10E9/l. Hydroxyurea use is permitted to meet this criterion
• Adequate renal function as demonstrated by a calculated creatinine clearance ≥ 30 mL/min; determined by the Cockcroft Gault formula.
• Adequate liver function as demonstrated by
• alanine aminotransferase (ALT) ≤ 4.0 × ULN.
• bilirubin ≤ 1.5 × ULN.
• ≥ 70 years of age OR
• ≥ 18 to 69 years of age and ineligible for intensive chemotherapy meeting at least one of the following criteria:
• Clinically significant comorbidities, as reflected by at least 1 of the following criteria:

You may not qualify if:

• Acute promyelocytic leukemia (APL).
• Patients with 4th or higher AML relapse.
• Leukemic cell content (blast percentage) in bone marrow/peripheral blood \< 10 %.
• ECOG \>3.
• Prior venetoclax treatment for myeloid malignancy.
• AML patients with CNS involvement (note: cerebrospinal fluid or radiological investigations are not required without clinical suspicion).
• HIV infection or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection that is not controlled with antiviral medication with the definition hereof at the discretion of the investigator.
• Cardiovascular disability status of New York Heart Association Class ≥ 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in palpitations, fatigue, dyspnea, or anginal pain.
• Evidence of clinically significant condition(s), which at the investigator's discretion would adversely affect the patient's participation in this study (including but not limited to):
• Chronic respiratory disease that requires continuous oxygen use.
• Systemic uncontrolled infection requiring therapy (viral, bacterial or fungal).
• Malabsorption syndrome or other condition that precludes enteral route of administration.
• Uncontrolled GVHD.
• Previous malignancies with the exception of previous malignancy treated successfully with curative intent and indolent/smoldering malignancies (defined at the investigator's discretion).
• Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment).

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Helse Stavanger HF: collaborator
• University Hospital of North Norway: collaborator
• Haukeland University Hospital: collaborator
• St. Olavs Hospital: collaborator
• Vestre Viken Hospital Trust: collaborator
• Helse Møre og Romsdal HF: collaborator
• Karolinska University Hospital: collaborator
• Skane University Hospital: collaborator
• Uppsala University Hospital: collaborator
• Helsinki University Central Hospital: collaborator
• Oulu University Hospital: collaborator
• Tampere University Hospital: collaborator
• Kuopio University Hospital: collaborator

Study Sites (1)

Department of Hematology, Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Kim Theilgaard-Mönch, MD, DMSc

CONTACT

+4535455197; kim.theilgaard-moench@regionh.dk

Anne Louise Tølbøll Sørensen, MD, PhD

CONTACT

+4535451864; anne.louise.toelboell.soerensen@regionh.dk

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: MD, DMSc

Study Record Dates

• First Submitted: June 1, 2022
• First Posted: June 24, 2022
• Study Start: May 24, 2022
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: June 24, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)