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

NCT03519984 | Terminated Phase 1 DMC FDA Drug

• 3 other identifiers: 9L-17-15NCI-2018-00680P30CA014089
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Blasts 5 Percent or More of Bone Marrow Nucleated Cells; Myelodysplastic/Myeloproliferative Neoplasm; Philadelphia Chromosome Positive; 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

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and summarized for each course separately.

  Up to 24 months

• Best clinical response in the blood and bone marrow observed at anytime during single agent treatment with recombinant EphB4-HSA fusion protein alone

  Best clinical response defined as complete remission (CR) + complete remission with incomplete blood count recovery (CRi) + partial remission (PR) + partial remission with incomplete blood count recovery (PRi). CR defined as Neutrophils: \>1,000/µL; Platelets: \>100,000/µL; Bone Marrow Blasts: \<5% with spicules, no Auer rods; Other: Transfusion independent, no extra medullary disease. CRi defined as Neutrophils: \<1,000/µL; Platelets: \<100,000/µL; Bone Marrow Blasts: \<5%; Other: Either neutrophils or platelets not recovered, no extra medullary disease. PR defined as Neutrophils: \>1,000/µL; Platelets: \>100,000/µL; Bone Marrow Blasts: decrease to 5-25 and = \> 50% decrease from start. PRi defined as Neutrophils: \<1,000/µL; Platelets: \<100,000/µL; Bone Marrow Blasts: decrease to 5-25 and = \> 50% decrease from start.

  Up to 24 months

• Complete remission (CR) and complete remission with incomplete blood count recovery (CRi) observed at anytime for the combination with cytarabine or liposomal vincristine

  CR defined as Neutrophils: \>1,000/µL; Platelets: \>100,000/µL; Bone Marrow Blasts: \<5% with spicules, no Auer rods; Other: Transfusion independent, no extra medullary disease. CRi defined as Neutrophils: \<1,000/µL; Platelets: \<100,000/µL; Bone Marrow Blasts: \<5%; Other: Either neutrophils or platelets not recovered, no extra medullary disease.

  Up to 24 months

Secondary Outcomes (1)

• Progression-free survival (PFS)

  Up to 24 months

Study Arms (2)

Arm A (sEPHB4-HSA, cytarabine)

EXPERIMENTAL

Participants receive recombinant EphB4-HSA fusion protein 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.

Drug: Cytarabine; Other: Laboratory Biomarker Analysis; Biological: Recombinant EphB4-HSA Fusion Protein

Arm B (sEPHB4-HSA, vincristine liposomal)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Biological: Recombinant EphB4-HSA Fusion Protein; Drug: Vincristine Liposomal

Interventions

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm A (sEPHB4-HSA, cytarabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (sEPHB4-HSA, cytarabine); Arm B (sEPHB4-HSA, vincristine liposomal)

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Arm A (sEPHB4-HSA, cytarabine); Arm B (sEPHB4-HSA, vincristine liposomal)

Vincristine Liposomal DRUG

Given IV

Also known as: Lipid-Encapsulated Vincristine, Liposomal Vincristine, Onco TCS, Vincacine, VincaXome, Vincristine Liposome, Vincristine, Liposomal

Arm B (sEPHB4-HSA, vincristine liposomal)

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of relapsed or refractory acute leukemia (acute myeloid leukemia, acute lymphoblastic leukemia, blast crisis of chronic myeloid leukemia \[CML\], secondary AML from prior myelodysplastic syndrome \[MDS\] / myeloproliferative neoplasm \[MPN\]); minimum of 5% blasts in the bone marrow or 10% blasts in circulation
• Patients with Philadelphia chromosome (Ph)+ ALL or blast crisis of CML must be refractory (not intolerant) to at least 2 second/third generation ABL kinase inhibitors (TKI)
• For AML: patients must belong to one of the following ?high risk? categories:
• Primary induction failure (PIF) as defined by failure to achieve at least a 50% reduction in bone marrow blasts after one cycle of high intensity, anthracycline containing induction regimen or failure to achieve complete response (CR)/complete remission with incomplete blood count recovery (CRi) after two cycles of high intensity chemotherapy
• First early relapse as defined by an initial remission duration of fewer than 6 months
• Second or subsequent relapse regardless of remission duration, or
• Relapse after allogeneic or autologous stem cell transplantation (first relapse after stem cell transplant would be eligible, regardless of prior duration of remission)
• Patients with MDS who transform to AML while on hypomethylator agents or patients with AML who progress on hypomethylator agents could be considered for arm A of this trial if
• They choose not to be treated on or are ineligible for the investigator's competing trial of sEPHB4-HSA + hypomethylator (9L-16-6)
• They are appropriate for high dose cytarabine treatment
• For ALL: patients must belong to one of the following ?high risk? categories:
• Primary refractory as defined by failure to achieve CR after induction and at least one salvage therapy
• Second or subsequent relapse
• Relapse after allogeneic or autologous stem cell transplantation (requirement for second relapse does not apply post-transplant)
• All variants of ALL including T-ALL, B / myeloid, lymphoblastic leukemia lymphoma are eligible

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (M3 classification)
• ALL patient refractory to their first induction only or their first relapse, will be excluded; they must be refractory to at least one salvage therapy, or relapse after first salvage, to be eligible
• ALL patients refractory to liposomal vincristine as defined by progression while on therapy or relapse within 3 months of completion of therapy with liposomal vincristine
• Prior malignancy requiring therapy within the last 12 months (excluding non-melanoma skin cancer); hormone therapy for prostate cancer or adjuvant endocrine therapy for breast cancer would not be excluded
• Patient is receiving other investigational agents
• Active central nervous system (CNS) disease
• Definition: any patient receiving active CNS therapy (defined as more than 1 intrathecal treatment per week or current radiation therapy to brain); if patient has a history of CNS disease: must have cerebrospinal fluid (CSF) sampling within 28 days of enrollment that is negative for leukemia; intrathecal chemotherapy for patients without active CNS disease is allowed (e.g., ongoing primary or secondary prophylaxis for patients who cleared the CSF prior to study enrollment); CSF sample is not required for enrollment for patients with no history of CNS disease
• Chemotherapy within 2 weeks of first dose of sEPHB4-HSA (minimum of 6 weeks for nitrosoureas and 8 weeks for bone marrow transplantation) with the following exceptions:
• Hydroxyurea allowed prior to, and up to day +5 of cycle 0 of treatment (max 100 mg/kg/day)
• Corticosteroids allowed until day -3 (max dexamethasone 20mg/day)
• Maintenance chemotherapy for ALL allowed one week prior to start of treatment (e.g., POMP)
• Grade ? 2 toxicity (other than alopecia) continuing from prior anticancer therapy, including radiation
• Patients with Charcot-Marie-Tooth disease or other demyelinating diseases are excluded from the liposomal vincristine containing arm
• New York Heart Association class 3 or 4 heart failure; myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEPHB4-HSA or places the patient at undue risk for treatment related complications
• Uncontrolled active systemic infections

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator
• Vasgene Therapeutics, Inc: collaborator
• Whittier Foundation: collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Myelodysplastic-Myeloproliferative Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cytarabine; Vincristine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Akil Merchant, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2018
• First Posted: May 9, 2018
• Study Start: May 9, 2018
• Primary Completion: November 24, 2020
• Study Completion: November 24, 2020
• Last Updated: November 30, 2021

Record last verified: 2021-11

Locations

US (1)