Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03146871
Other study ID # 9L-16-6
Secondary ID NCI-2017-006239L
Status Terminated
Phase Phase 2
First received
Last updated
Start date April 20, 2017
Est. completion date March 27, 2019

Study information

Verified date April 2019
Source University of Southern California
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

PRIMARY OBJECTIVES:

I. To describe the toxicities and assess the tolerability of recombinant EphB4-HSA fusion protein (sEphB4-HSA) in combination with an approved hypomethylating agent (HMA) among patients with myelodysplastic syndrome (MDS) who are refractory to or have lost their response to one or more HMAs and among patients with relapsed/refractory acute myeloid leukemia (AML) previously treated with a HMA.

SECONDARY OBJECTIVES:

I. To measure the expression of EphB4 among marrow and peripheral blood blasts in patients with MDS & AML at baseline and over the course of treatment.

II. To measure the expression of immune check-point activating ligands (such as PD-L1, PD-L2) on marrow and peripheral blood blasts in patients treated with HMA and sEphB4-HSA in combination.

III. To profile immune subsets (activated and exhausted T cells, natural killer [NK] cells, T regulatory cells, and myeloid derived suppressor cells) in the peripheral blood and marrow in patients treated with HMA and sEphB4-HSA in combination.

IV. To assess efficacy of sEphB4-HSA in combination with an HMA as manifest by International Working Group (IWG) response criteria, as well as time to development of acute myeloid leukemia (AML) in patients with MDS and time to progression.

OUTLINE:

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1 and 15. Patients also receive azacitidine IV or subcutaneously (SC) on days 1-7 or days 1-5 and 8-9, or decitabine IV on days 1-5. 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.

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


Recruitment information / eligibility

Status Terminated
Enrollment 7
Est. completion date March 27, 2019
Est. primary completion date March 19, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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

- During the 8 weeks prior to inclusion in study, subjects must have a baseline bone marrow examination including all of the following:

- 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

- Women of childbearing potential (WOCBP) and male patients with WOCBP as partners must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of the investigational agent; subject is practicing an acceptable method of contraception (documented in case report form [CRF]); WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal; post menopause is defined as:

- Amenorrhea >= 12 consecutive months without another cause or

- For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL

- Women who are using oral contraceptives, other hormonal contraceptives (vagina products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential

- WOCBP must have a negative serum test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the start of investigational product

- Patients with uncontrolled hypertension

Exclusion Criteria:

- 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

- MEDICATION-RELATED EXCLUSION CRITERIA

- Patients with uncontrolled hypertension (HTN) (> 160/90) will not be admitted onto the study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Azacitidine
Given IV or SC
Decitabine
Given IV
Other:
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Biological:
Recombinant EphB4-HSA Fusion Protein
Given IV

Locations

Country Name City State
United States USC / Norris Comprehensive Cancer Center Los Angeles California

Sponsors (2)

Lead Sponsor Collaborator
University of Southern California National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in the percent of bone marrow and peripheral blood blasts expressing EphB4 assessed by flow cytometry Baseline up to 3 years
Other T-cell subset profile assessed by flow cytometry Baseline up to 3 years
Primary Incidence of adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 Will be tabulated and reported according to grade, type, cycle, and attribution. Up to 30 days of the last dose of protocol treatment
Primary Overall response defined as the occurrence of complete response, marrow complete response, partial response, or hematological improvement assessed by the IWG Working Group Criteria for MDS and AML Will be calculated based on all patients who began treatment; exact 95% confidence intervals will be constructed. Up to 56 days (2 courses of protocol treatment)
Primary Time to death from any cause Will be displayed with Kaplan-Meier plots. From start of treatment to death from any cause, assessed for up to 3 years
Primary Time to disease progression Will be displayed with Kaplan-Meier plots. From the start of treatment to the first disease progression or recurrence, assessed for up to 3 years
Primary 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 4 weeks following completion of course 2
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Active, not recruiting NCT03289910 - Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia Phase 2
Recruiting NCT06159491 - Pacritinib in CMML Phase 1/Phase 2
Completed NCT01427881 - Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies Phase 2
Recruiting NCT01133886 - Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure Phase 2
Completed NCT01169012 - PK Study of Oral and IV Clofarabine in High Risk Myelodysplasia+Acute Leukemias Phase 1
Completed NCT01233921 - Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer N/A
Completed NCT01093586 - Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies Phase 2
Terminated NCT00509249 - Aflibercept in Treating Patients With Myelodysplastic Syndromes Phase 2
Terminated NCT00387426 - Sunitinib in Treating Patients With Idiopathic Myelofibrosis Phase 2
Completed NCT00096122 - Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia Phase 1/Phase 2
Completed NCT00171912 - Imatinib Mesylate in Patients With Various Types of Malignancies Involving Activated Tyrosine Kinase Enzymes Phase 2
Completed NCT00078858 - Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant Phase 1/Phase 2
Completed NCT00052520 - Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation Phase 1/Phase 2
Recruiting NCT03683433 - Enasidenib and Azacitidine in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia and IDH2 Gene Mutation Phase 2
Recruiting NCT04980404 - Inqovi Maintenance Therapy in Myeloid Neoplasms Phase 1
Active, not recruiting NCT03588078 - Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine Phase 1/Phase 2
Withdrawn NCT06085638 - Phase I/II Study of SY-1425 (Tamibarotene) in Combination With Azacitidine and Venetoclax for Patients With Chronic Myelomonocytic Leukemia Phase 1/Phase 2
Recruiting NCT03999723 - Combining Active and Passive DNA Hypomethylation Phase 2
Terminated NCT00852709 - Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias Phase 1