EphB4-HSA Fusion Protein and Cytarabine /or Liposomal Vincristine in Patients With Recurrent or Refractory Acute Leukemia

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

Official title: A Phase I Dose Escalation Study With Expansion to Evaluate the Safety of SEPHB4-HSA in Combination With Cytarabine or Liposomal Vincristine in Patients With Relapsed or Refractory Acute Leukemia

Status Terminated

Clinical Trial Summary

This phase I trial studies the side effects and best dose of recombinant EphB4-HSA fusion protein when given together with cytarabine or vincristine liposomal in treating participants with acute leukemia that has come back or has not responded to treatment. Drugs used in chemotherapy, such as recombinant ephb4-HSA fusion protein, cytarabine, and vincristine liposomal, 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. Giving the drugs in different combinations may kill more cancer cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. Characterize the DLTs (dose limiting toxicities) and overall toxicity profile of recombinant EphB4-HSA fusion protein (sEPHB4-HSA) as a single agent and in combination with cytarabine or liposomal vincristine in patients with acute leukemia.

SECONDARY OBJECTIVES:

I. Estimate the clinical response (including minimal residual disease [MRD]) in blood and bone marrow of sEPHB4-HSA in combination with cytarabine in patients with relapsed/refractory acute myeloid leukemia.

II. Estimate the clinical response (including MRD) in blood and bone marrow of sEPHB4-HSA in combination with liposomal vincristine in patients with relapsed/refractory acute lymphoid leukemia.

III. Estimate the single agent clinical response of sEPHB4-HSA in blood and bone marrow of patients with relapsed/refractory acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL).

IV. Assess pharmacokinetics of sEPHB4-HSA as a single agent and in combination with cytarabine or liposomal vincristine in patients with leukemia.

EXPLORATORY OBJECTIVES:

I. Estimate progression-free survival and overall survival in patients treated with sEPHB4-HSA in combination with cytarabine or liposomal vincristine.

II. Estimate percentage of patients proceeding to allogeneic stem cell transplantation.

III. Correlate expression of EPHB4 leukemic blasts and ephrinB2 in bone marrow microenvironment with response to sEPHB4-HSA.

IV. Evaluate the effect of sEPHB4-HSA on downstream protein mediators of the EPHB4 pathway (phosphorylated [p]AKT, pS6) on leukemic blasts and determine if these can be used as biomarkers of response to treatment.

V. Profile the immuno-modulatory effects of sEPHB4-HSA on peripheral blood leukocytes and in the tumor microenvironment.

OUTLINE: This is a dose-escalation study of recombinant EphB4-HSA fusion protein. Participants are randomized to 1 of 2 arms.

ARM A: Participants receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1, 8, 15, and 22 and cytarabine IV over 4 hours on days 1-5. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Participants receive recombinant EphB4-HSA fusion protein IV over 60 minutes on days 1, 8, 15, and 22 and vincristine liposomal IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up at 3 months. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
• Blasts 5 Percent or More of Bone Marrow Nucleated Cells
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm
• Myeloproliferative Disorders
• Philadelphia Chromosome
• Philadelphia Chromosome Positive
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia
• Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Secondary Acute Myeloid Leukemia
• T Acute Lymphoblastic Leukemia

• NCT number: NCT03519984
• Study type: Interventional
• Source: University of Southern California
• Status: Terminated
• Phase: Phase 1
• Start date: May 9, 2018
• Completion date: November 24, 2020