A Phase 2a, Open-Label, Two Stage Study of Nerofe or Nerofe With Doxorubicin in Subjects With AML or MDS

NCT03059615 | Withdrawn Phase 2 DMC

• 1 other identifier: ISK-N102
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 2a, Open-label, one arm study in which the eligible patients will be treated with IV Nerofe, three times a week in 28 days cycles (up to 12 cycles). Evaluation will include safety procedures, blood level of study drug in certain time points, immune system response and tests checking the mechanism of the drug action.

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (7)

• Assessing change in IWG Criteria to evaluate response to Nerofe treatment (with or without Doxorubicin) for AML subjects

  Bone Marrow samples and CBC will be done every 2 cycles

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Assessing changes in R-IPSS (Revised International Prognostic Scoring System) Score to evaluate response to Nerofe treatment (with or without Doxorubicin) for MDS patients. A calculation of several variables.

  Bone Marrow samples to measure percentage of blasts (%). Range 0-30% (the higher the percentage the worse outcome).

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Assessing changes in R-IPSS (Revised International Prognostic Scoring System) Score to evaluate response to Nerofe treatment (with or without Doxorubicin) for MDS patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure hemoglobin (g/dL). Range 4-20 (4 worse outcome and 20 best outcome).

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Assessing changes in R-IPSS (Revised International Prognostic Scoring System) Score to evaluate response to Nerofe treatment (with or without Doxorubicin) for MDS patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure absolute neutrophil count (x10\^9/L). Range 0-15 (the higher the score the better outcome).

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Assessing changes in R-IPSS (Revised International Prognostic Scoring System) Score to evaluate response to Nerofe treatment (with or without Doxorubicin) for MDS patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure platelets (x10\^9/L). Range 0-2000 (the higher the score the better outcome)

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Assessing changes in R-IPSS (Revised International Prognostic Scoring System) Score to evaluate response to Nerofe treatment (with or without Doxorubicin) for MDS patients. A calculation of several variables.

  Measuring cytogenetic abnormalities. Range from very good (0) to very poor (4)

  At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)

• Safety as determined by frequency, nature and severity of adverse events

  Per CTCAE v4.0

  13 months

Secondary Outcomes (7)

• Pharmacokinetic behavior of Nerofe: Maximum Plasma Concentration (Cmax)

  At cycles 1 and 2 (Cycle length 28 days)

• Pharmacokinetic behavior of Nerofe: Minimum Plasma Concentration (Cmin)

  At cycles 1 and 2 (Cycle length 28 days)

• Pharmacokinetic behavior of Nerofe: Area Under the Curve (AUC)

  At cycles 1 and 2 (Cycle length 28 days)

• Pharmacokinetic behavior of Nerofe: Tmax

  At cycles 1 and 2 (Cycle length 28 days)

• Pharmacodynamic analysis of changes from baseline in levels of circulating cytokines

  Every cycle (Cycle length 28 days)

Study Arms (4)

Nerofe 48mg/m2

EXPERIMENTAL

48mg/m2 IV Nerofe - three times a week

Drug: Nerofe

Nerofe 96mg/m2

EXPERIMENTAL

96mg/m2 IV Nerofe - three times a week

Drug: Nerofe

Nerofe 48mg/m2 + Doxorubicin 10mg/m2

EXPERIMENTAL

48mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week

Drug: Nerofe; Drug: Doxorubicin

Nerofe 96mg/m2 + Doxorubicin 10mg/m2

EXPERIMENTAL

96mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week

Drug: Nerofe; Drug: Doxorubicin

Interventions

Nerofe DRUG

Nerofe is a first-in-class hormone-peptide with cancer suppressive properties. Nerofe is a derivative of the human hormone-peptide Tumor-Cells Apoptosis Factor (TCApF). It contains 14 amino-acids. Binding Nerofe to the T1/ST2 receptor caused a rapid activation both of Caspase 8 and Bcl-2 mediated downstream in proliferating cancer cells.

Nerofe 48mg/m2; Nerofe 48mg/m2 + Doxorubicin 10mg/m2; Nerofe 96mg/m2; Nerofe 96mg/m2 + Doxorubicin 10mg/m2

Doxorubicin DRUG

Doxorubicin is an anthracycline antibiotic with antineoplastic activity. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. Doxorubicin intercalates between base pairs in the DNA helix, thereby preventing DNA replication and ultimately inhibiting protein synthesis.

Nerofe 48mg/m2 + Doxorubicin 10mg/m2; Nerofe 96mg/m2 + Doxorubicin 10mg/m2

Eligibility Criteria

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

You may qualify if:

• Males and females ≥18 years of age.
• Either:
• AML patients, who are not candidates for aggressive therapy and/or stem cell transplant (usually the elderly patients), or
• Low and high prognostic risk MDS patients (according to the IPSS-R classification), resistant or relapsing following at least 1 course of hypo-methylation therapy.
• Anti-tumor (in this case the anti-MDS or anti-leukemic) effect can be measured according to the IWG criteria (Appendices B, C).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Acceptable clinical laboratory values at screening, as indicated by:
• Absolute neutrophil count ≥ 1,000/mm3;
• Platelets ≥ 50,000/mm3;
• Hemoglobin ≥ 6.5 g/dl ;
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN);
• AST (SGOT) ≤ 2.5 × the ULN;
• ALT (SGPT) ≤ 2.5 × the ULN;
• Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance 60 mL/min and above
• Negative serum β hCG test in women of childbearing potential

You may not qualify if:

• Any chemotherapy, immunomodulatory drug therapy, anti-neoplastic hormonal therapy 30 days prior to study entry and , immunosuppressive therapy, prednisone \> 20 mg/day, or any equivalent corticosteroids during the last six months.
• Erythroid stimulating agents are allowed until one day prior to treatment initiation with study drug.
• Presence of an acute toxicity of prior chemotherapy, with the exception of alopecia or peripheral neuropathy, that has not resolved to ≤ Grade 2, as determined by NCI CTCAE v 4.0
• Receipt of \>1 prior regimen of genotoxic therapy.
• Previous bone marrow transplantation.
• Life expectancy \<12 weeks.
• RBC transfusions for at least 1 week and platelet transfusions for at least 3 days prior to study entry.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).
• Known active hepatitis B or C or other active liver disease
• Active infection requiring systemic therapy.
• Unstable Insulin-dependent diabetes mellitus (IDDM), defined by one or more hospitalization (including ER visits) due to high or low blood glucose levels within the last 6 months.
• History of any of the following within 12 months prior to initiation of study drug: Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), unstable angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism (within the last 6 month).
• Uncontrolled hypertension and change in treatment regimen within the last month prior to screening.
• Risk of syncope, in the judgment of the Principle Investigator, according to the patient's history of Syncope.
• History of ongoing cardiac dysrhythmias requiring drug treatment.

Sponsors & Collaborators

• Immune System Key Ltd: lead

Study Sites (2)

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

tumor-cells apoptosis factor, human; Doxorubicin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Yoram Devary

  Immune System Key Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 stage study: 1. Dose Range Finder (4 treatment arms) 2. Dose Confirmation (1 chosen treatment arm)

Study Record Dates

• First Submitted: February 9, 2017
• First Posted: February 23, 2017
• Study Start: October 25, 2018
• Primary Completion: July 26, 2020
• Study Completion: July 26, 2020
• Last Updated: July 31, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)