Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia

Secondary Acute Myeloid Leukemia Clinical Trial

Official title: Phase Ib/II Study of Uproleselan Added to Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed by Consolidation With Uproleselan Plus Cladribine Plus LDAC in Patients With Treated Secondary AML (TS-AML)

Status Active, not recruiting

Clinical Trial Summary

This phase Ib/II trial finds out the best dose and effect of cladribine and low dose cytarabine when given in combination with uproleselan in treating patients with treated secondary acute myeloid leukemia. Chemotherapy drugs, such as uproleselan, cladribine, and low dose cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To determine the safety, tolerability, and recommended phase II dose (RP2D) of uproleselan combined with cladribine + low dose cytarabine (LDAC) in patients with treated-secondary acute myeloid leukemia (AML) (ts-AML).

SECONDARY OBJECTIVES:

I. To assess the efficacy (overall response rate [ORR], complete response [CR], complete response without blood count recovery [CRi], CR with partial hematologic recovery [CRh], partial response [PR], or morphologic leukemia-free state of uproleselan combined with cladribine + LDAC in patients with ts-AML.

II. To assess the rate of minimal residual disease (MRD) negativity by flow cytometry at response.

III. To assess overall survival (OS), remission duration (CRd), and progression-free survival (PFS) in patients with ts-AML treated with uproleselan combined with cladribine + LDAC.

IV. To assess the rate of complete cytogenetic response (CCyR) in patients with ts-AML with abnormal baseline karyotype, treated with uproleselan combined with cladribine + LDAC.

V. To assess toxicity and induction mortality of patients with AML treated with uproleselan added to cladribine + LDAC.

EXPLORATORY OBJECTIVES:

I. To explore biomarkers of response and resistance in patients with ts-AML treated with uproleselan combined with cladribine + LDAC.

II. To examine the correlation of E-selectin ligand-forming glycosylation genes of leukemic blasts with clinical outcome.

OUTLINE: This is a phase I, dose-escalation study of cladribine and cytarabine followed by a phase II study.

INDUCTION THERAPY: Patients receive uproleselan intravenously (IV) over 20 minutes on day 1 and every (Q) 12 hours on days 2-12, cladribine IV over 1-2 hours on days 1-5 and cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 in the absence of disease progression or unacceptable toxicity. Patients who do not achieve a CR or CRi after cycle 1 may receive a second induction cycle.

CONSOLIDATION/MAINTENANCE THERAPY: Patients receive uproleselan IV over 20 minutes on day 1 and Q12 hours on days 2-1. Patients who have achieved at least CR/CRi or morphologic leukemia-free state after induction therapy receive uproleselan IV once daily (QD) on days 1-12. Patients also receive cladribine IV over 1-2 hours on days 1-3 and cytarabine SC BID on days 1-10. Treatment repeats every 4 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6-12 months. ;

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Neoplasm Metastasis
• Secondary Acute Myeloid Leukemia

• NCT number: NCT04848974
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 11, 2021
• Completion date: December 31, 2026