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Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia | Clinical Trials | Clareo Health

WITHDRAWNPHASE1

Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT06007911•Medical College of Wisconsin

View on ClinicalTrials.gov

Summary

This is an open-label phase I study designed to evaluate the safety of venetoclax-navitoclax with cladribine-based salvage therapy.

Detailed Description

The primary objective of the study is to determine a maximum-tolerated dose (MTD) combination of venetoclax-navitoclax with cladribine-based salvage therapy. Subjects will be entered sequentially to each dose level. For each dose level, if none of the first three subjects at that level experiences a dose-limiting toxicity (DLT), new subjects may be entered at the next higher dose level. If one of three subjects experience a DLT, up to three more subjects are to be treated at that same dose level. If none of the additional three subjects at that dose level experiences a DLT, new subjects may be entered at the next higher dose level. However, if one or more of the additional three subjects experience a DLT, then no further subjects are to be started at that dose level and either de-escalate one level or if the preceding dose is already completed then that dose is the MTD. The MTD will be defined as the highest dose level at which none of the first three treated subjects, or no more than one of the first six treated subjects, experiences a DLT.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Male or female subjects 18 years or older.
•2. Patients must have a diagnosis of morphologically documented AML or secondary AML from prior conditions, such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), MDS/MPN, chronic myelomonocytic leukemia (CMML) or therapy-related AML (t-AML), as defined by the World Health Organization (WHO) 2022 criteria.
•3. Relapsed or refractory to at least one prior line of therapy.
•4. Previous therapy with venetoclax.
•5. Eastern Cooperative Oncology Group (ECOG) performance status of:
•1. 0-3 for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).
•2. 0-2 for Arm B (i.e., CLAG-M backbone arm).
•6. Left ventricular ejection fraction (LVEF) of:
•1. LVEF ≥35% for Arm A (i.e., Cladribine-low dose cytarabine backbone arm).
•2. LVEF ≥45% for Arm B (i.e., CLAG-M backbone arm).
+17 more criteria

Exclusion Criteria

•1. Acute promyelocytic leukemia.
•2. Prior therapy with B-cell lymphoma-extra large (BCL-XL) inhibitor.
•3. Treatment with systemic antineoplastic therapy within 14 days or five half-lives from the last dose - whichever is longer - before Cycle 1, Day 1 of therapy. Radiation within 14 days before Cycle 1, Day 1 of therapy. The use of hydroxyurea/cytarabine for leukoreduction is permitted.
•4. Hematopoietic stem cell transplantation (HCT) or chimeric antigen receptor T-cell therapy (CAR-T cell) within 60 days of enrollment. (If patients had prior allogeneic HCT, they should have no active graft-versus-host disease and should be off calcineurin inhibitors at least four weeks prior to cycle 1 day 1 of therapy.)
•5. Current systemic treatment with strong or moderate Cytochrome P4503A (CYP3A) inducers within 7 days prior to Cycle 1, Day 1 of therapy.
•6. Presence of another active malignancy requiring systemic treatment within the last 12 months, except for localized cancers that have been adequately treated.
•7. Known HIV positive patients who DO NOT meet the following criteria:
•1. Cluster of differentiation (CD) 4 count \> 350 cells/mm\^3.
•2. Undetectable viral load.
•3. Maintained on modern therapeutic regimens utilizing non-CYP-interactive agents.
+6 more criteria

Locations (1)

Froedtert Hospital & the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Key Dates

Start Date

August 31, 2024

Primary Completion Date

December 1, 2025

Completion Date

April 1, 2027

Last Updated

August 13, 2024

Conditions

Relapsed Adult AMLRefractory AML

Interventions

Navitoclax Dose Level -1

DRUG

Navitoclax Dose Level 0

DRUG

Navitoclax Dose Level 1

DRUG

Navitoclax Dose Level 2

DRUG

Venetoclax Dose Level -1

DRUG

Venetoclax Dose Levels 0 to 2

DRUG

Cladribine

DRUG

Cytarabine (Cladribine Low Dose Cytarabine Backbone)

DRUG

Cytarabine (CLAG-M Backbone)

DRUG

Mitoxantrone

DRUG

Granulocyte Colony-Stimulating Factor

DRUG

Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: August 13, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Inclusion Criteria

Exclusion Criteria

Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia

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