Recombinant EphB4-HSA Fusion Protein and Azacitidine or Decitabine for Relapsed or Refractory Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia Patients Previously Treated With a Hypomethylating Agent

NCT03146871 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 9L-16-6NCI-2017-00623P30CA014089
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This trial studies the side effects of recombinant EphB4-HSA fusion protein when given together with azacitidine or decitabine in treating patients with myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia that has come back or has not responded to previous treatment with a hypomethylating agent. Recombinant EphB4-HSA fusion protein may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hypomethylating agents, such as azacitidine and decitabine, slow down genes that promote cell growth and can kill cells that are dividing rapidly. Giving recombinant EphB4-HSA fusion protein together with azacitidine or decitabine may work better in treating patients with myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia.

Conditions

Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Recurrent Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (5)

• Assessment of Toxicity to Hypomethylating Agent (HMA)

  Toxicity will be assessed and graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0, after each cycle.

  Up to 13 months (up to 12 cycles + 30 days) from the start of treatment.

• Overall Response Defined as the Occurrence of Complete Response, Marrow Complete Response, Partial Response, or Hematological Improvement

  Responses assessed by the International Working Group (IWG) 2023 criteria are a set of standardized guidelines used to assess treatment response in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). These criteria are designed to evaluate a patient's response based on hematologic improvements, such as changes in blood counts and transfusion independence.

  Up to 56 days (2 courses of protocol treatment)

• Time to Death From Any Cause

  Will be displayed with Kaplan-Meier plots.

  up to 1 year (12 cycles)

• Time to Disease Progression

  This will be measured from the start of treatment to the first disease progression or recurrence. Patients who are progression free at the time of last follow-up will be censored; death prior to progression will be counted as an event.

  up to 1 year (12 cycles)

• Tolerability Defined as the Ability to Complete Two Courses of Treatment Without the Occurrence of Dose Limiting Toxicity and the Ability to Begin Course 3 Within 4 Weeks and Graded According to the NCI CTCAE v4.0

  Will be tabulated and reported according to grade, type, cycle, and attribution.

  Up to 3 months

Other Outcomes (2)

• Change in the Percent of Bone Marrow and Peripheral Blood Blasts Expressing EphB4 Assessed by Flow Cytometry

  At Baseline, then up to 3 years.

• T-cell Subset Profile Assessed by Flow Cytometry

  At Baseline, then up to 2 years.

Study Arms (1)

Treatment (sEphB4-HSA, azacitidine, decitabine)

EXPERIMENTAL

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes at a dose of 15mg/kg on days 1 and 15 of a 28-day cycle. Patients also receive azacitidine IV or subcutaneously (SC) at a dose of 75mg/m2 on days 1-7 or days 1-5 and 8-9 on a 28-day cycle, or decitabine IV at a dose of 20 mg/m2 on days 1-5 on a 28-day cycle. Administration of recombinant EphB4-HSA fusion protein occurs before or after the HMA (not concurrently). Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Decitabine; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Recombinant EphB4-HSA Fusion Protein

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (sEphB4-HSA, azacitidine, decitabine)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (sEphB4-HSA, azacitidine, decitabine)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (sEphB4-HSA, azacitidine, decitabine)

Pharmacological Study OTHER

Correlative studies

Treatment (sEphB4-HSA, azacitidine, decitabine)

Recombinant EphB4-HSA Fusion Protein BIOLOGICAL

Given IV

Also known as: sEphB4-HSA

Treatment (sEphB4-HSA, azacitidine, decitabine)

Eligibility Criteria

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

You may qualify if:

• Adult subjects with advanced MDS requiring treatment with HMA and either refractory to at least 4 cycles or progressing after previously documented response
• Patient must be treated within 6 months of the last HMA treatment and must be willing to be treated with the same agent they last received on this study
• Prior treatment with novel HMA analog of decitabine on clinical trial is allowed; in such cases, decitabine will be used as the standard of care agent
• MDS classified as intermediate 1-risk or high risk according to the international prognostic scoring system (IPSS) or revised-IPSS
• Chronic myelomonocytic leukemia (CMML)
• Acute myeloblastic leukemia (AML) that was previously treated with HMA and is unfit for intensive chemotherapy
• Patient must be within 6 months of prior treatment with HMA and must be willing to be treated with the same agent on this study
• Cytomorphology to confirm bone marrow blasts
• Cytogenetics
• Eastern Cooperative Oncology Group (ECOG) status 0-2
• Subject is able to understand and willing to comply with protocol requirements and instructions
• Subject has signed and dated informed consent
• Total bilirubin (except for Gilbert's syndrome) =\< 2.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
• Creatinine =\< 2.5 x ULN

You may not qualify if:

• Patients with AML whose white blood cell count exceeds 25,000
• Corrected QT (QTc) (Fridericia Correction Formula) \> 480 on electrocardiogram (ECG)
• Patients whose electrolytes (sodium, potassium, calcium, magnesium) are abnormal or cannot be normalized with standard intervention on the day of treatment with study drug
• Patients who are actively receiving any other anticancer therapy
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to HMAs
• Patients with a diagnosis of acute promyelocytic leukemia
• Patients with short life expectancy (less than 3 months) due to comorbidity other than MDS
• Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotropin \[B-hCG\] pregnancy test)
• Patients with current alcohol or drug abuse
• Patients who have received treatment with an investigational drug within 30 days preceding the first dose of study medication
• Patients with uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients infected with hepatitis B, C or human immunodeficiency virus (HIV), unless they are on stable and effective antiviral treatment
• Patients with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization; inhaled or topical steroids and adrenal replacement steroid doses \> 10mg daily prednisone equivalent, are permitted in the absence of uncontrolled autoimmune disease
• Patients with uncontrolled hypertension (HTN) (\> 160/90) will not be admitted onto the study

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Acute

Interventions

Azacitidine; Decitabine; Injections

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Victoria Soto, Clinical Research Regulatory Administrator
• Organization: USC Norris Comprehensive Cancer Center

Victoria.Soto@med.usc.edu

(323) 865-0454

Study Officials

• Casey O'Connell, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 10, 2017
• Study Start: April 20, 2017
• Primary Completion: March 19, 2019
• Study Completion: March 27, 2019
• Last Updated: June 8, 2026
• Results First Posted: June 8, 2026

Record last verified: 2025-12

Locations

US (1)