Study to Evaluate Imetelstat in Patients With High-Risk MDS or AML Failing HMA-based Therapy

NCT05583552 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IMpress_001
• Study Type: interventional
• Target: 46
• Locations: 3 countries
• Sites: 11

Brief Summary

The purpose of this study is to evaluate the efficacy, in terms of hematologic improvement, and safety of imetelstat in participants with high-risk (HR) myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that is relapsed/refractory to hypomethylating agents (HMAs) treatment. Responding patients are eligible to continue treatment until loss of response/disease progression.

Conditions

Myelodysplastic Syndromes; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Hematological Response Rate of Participants after Treatment with Imetelstat

  The combined response assessment criteria for MDS and AML based on IWG 2018 criteria (MDS) and the criteria of the European LeukemiaNet (AML) will be used to define responders. The response rate is calculated as number of responders divided by the number of all participants of the analysis set.

  After 4 Months of Treatment

Study Arms (1)

Single-arm imetelstat

EXPERIMENTAL

Drug: Imetelstat sodium

Interventions

Imetelstat sodium DRUG

Intravenous injection

Also known as: GRN163L

Single-arm imetelstat

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent
• Male and female ≥ 18 years at the first screening
• Must be able to adhere to the study visit schedule and other protocol requirements
• Initial diagnosis of AML or MDS according to WHO 2016 classification
• At least one cytopenia
• Failure to achieve complete or partial response or hematological improvement observed after at least six azacitidine monotherapy or four decitabine monotherapy based 4-week treatment cycles administered during the past two years OR Failure to achieve complete or partial response or hematological improvement observed after at least two 4-week treatment cycles with azacitidine plus venetoclax or with decitabine plus venetoclax during the past two years OR Relapse after initial complete or partial response or hematological improvement observed after at least six (azacitidine) or four (decitabine) based 4-week treatment cycles administered during the past two years OR Relapse after initial complete or partial response or hematological improvement observed after at least two 4-week treatment cycles with azacitidine plus venetoclax or with decitabine plus venetoclax during the past two years OR Intolerance to treatment with HMA-based therapy during the past two years
• Not eligible for allogeneic stem cell transplantation
• ≥ 5% bone marrow blasts at screening
• Off all other treatments for AML/MDS for at least 14 days; granulocyte colony-stimulating factor (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Biochemical laboratory test values must be within the defined limits.
• Availability of blood counts and transfusion events for previous 16 weeks
• Women of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies. For females, these restrictions apply for 3 months after the end of dosing.
• A woman of childbearing potential must have a negative serum or urine pregnancy test at screening and agree to be tested on day 1 of every cycle and at End of Treatment (EOT)
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control. For males, these restrictions apply for 3 months after the end of dosing

You may not qualify if:

• Chemotherapy within the 14 days prior to the first dose of imetelstat being administered (other than hydroxyurea)
• Participant has known allergies, hypersensitivity, or intolerance to imetelstat or its excipients (refer to the Investigators Brochure (IB))
• Participant has received an experimental or investigational drug or used an invasive investigational medical device within 30 days prior to day 1 of Cycle 1
• Prior treatment with imetelstat
• Prior history of intensive chemotherapy or hematopoietic stem cell transplant
• Major surgery within 4 weeks prior to day 1 of Cycle 1 (excluding the placement of vascular access and other minor surgical procedures)
• Diagnosed or treated for malignancy other than MDS or AML, except:
• Malignancy treated with curative intent and with no known active disease present for 3 years before day 1 of Cycle 1 Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease Adequately treated cervical carcinoma in situ without evidence of disease
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of day 1 of Cycle 1, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known history of human immunodeficiency virus (HIV) or any uncontrolled active systemic infection requiring IV antibiotics
• Active systemic hepatitis infection requiring treatment (carriers of hepatitis virus are permitted to enter the study), or known acute or chronic liver disease including cirrhosis
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the participant 's safety, interfere with the imetelstat metabolism, or put the study outcomes at undue risk; Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Females who are pregnant or are currently breastfeeding or planning to become pregnant while enrolled in this study or within 3 months after the end of dosing
• Participant is a man who plans to father a child while enrolled in this study or within 3 months after the end of dosing
• Other:

Sponsors & Collaborators

• GCP-Service International West GmbH: lead
• Geron Corporation: collaborator
• Universitätsklinikum Leipzig: collaborator
• Saint-Louis Hospital, Paris, France: collaborator
• QIMR Berghofer Medical Research Institute: collaborator
• Australasian Leukaemia and Lymphoma Group: collaborator
• Groupe Francophone des Myelodysplasies: collaborator
• German Myelodysplastic Syndrome Study Group: collaborator

Study Sites (11)

Royal Adelaide Hospital

Adelaide, Australia

Location

Royal Brisbane and Women's Hospitals

Brisbane, Australia

Location

Linear Clinical Research

Nedlands, Australia

Location

CHU Nantes - Hôtel Dieu

Nantes, France

Location

Hôpital Archet 1

Nice, France

Location

Hôpital Saint-Louis

Paris, France

Location

CHU de Toulouse

Toulouse, France

Location

Marien Hospital Düsseldorf

Düsseldorf, Germany

Location

Universität Jena, Medizinische Fakultät

Jena, Germany

Location

Universität Leipzig, Medizinische Fakultät

Leipzig, Germany

Location

Klinikum rechts der Isar

München, Germany

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes; Leukemia, Myeloid, Acute

Interventions

imetelstat; GRN163L peptide

Condition Hierarchy (Ancestors)

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

Study Officials

• Uwe Platzbecker, MD

  Universitätsklinikum Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 17, 2022
• Study Start: June 5, 2023
• Primary Completion: September 30, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 14, 2025

Record last verified: 2024-06

Locations

AU (3); DE (4); FR (4)