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Trial record 3 of 3 for:    nerofe

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

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ClinicalTrials.gov Identifier: NCT03059615
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : August 28, 2018
Sponsor:
Information provided by (Responsible Party):
Immune System Key Ltd

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.


Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Myelodysplastic Syndromes Drug: Nerofe Drug: Doxorubicin Phase 2

Detailed Description:
Nerofe is a first-in-class hormone peptide with cancer suppressive properties. It works in three mechanisms of action. The purpose of this research is to study Nerofe's effect in patients diagnosed with AML and MDS.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 29 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

2 stage study:

  1. Dose Range Finder (4 treatment arms)
  2. Dose Confirmation (1 chosen treatment arm)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a, Open-Label, Two Stage Study: Stage A: Dose-Range Finder Study to Assess the Safety and Efficacy of Two Doses of Nerofe and Two Doses of Nerofe in Combination With Doxorubicin in Subjects With Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome (AML/High Risk MDS). Stage B: Dose Confirmation Study to Assess the Safety and Efficacy of Nerofe or Nerofe in Combination With Doxorubicin in Subjects With AML/ High Risk MDS
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Nerofe 48mg/m2
48mg/m2 IV Nerofe - three times a week
Drug: Nerofe
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.

Experimental: Nerofe 96mg/m2
96mg/m2 IV Nerofe - three times a week
Drug: Nerofe
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.

Experimental: Nerofe 48mg/m2 + Doxorubicin 10mg/m2
48mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week
Drug: Nerofe
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.

Drug: Doxorubicin
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.

Experimental: Nerofe 96mg/m2 + Doxorubicin 10mg/m2
96mg/m2 IV Nerofe + Doxorubicin 10mg/m2 - once a week
Drug: Nerofe
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.

Drug: Doxorubicin
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.




Primary Outcome Measures :
  1. Assessing change in IWG Criteria to evaluate response to Nerofe treatment (with or without Doxorubicin) for AML subjects [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Bone Marrow samples and CBC will be done every 2 cycles

  2. 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. [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Bone Marrow samples to measure percentage of blasts (%). Range 0-30% (the higher the percentage the worse outcome).

  3. 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. [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Complete Blood Count (CBC) to measure hemoglobin (g/dL). Range 4-20 (4 worse outcome and 20 best outcome).

  4. 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. [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Complete Blood Count (CBC) to measure absolute neutrophil count (x10^9/L). Range 0-15 (the higher the score the better outcome).

  5. 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. [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Complete Blood Count (CBC) to measure platelets (x10^9/L). Range 0-2000 (the higher the score the better outcome)

  6. 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. [ Time Frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days) ]
    Measuring cytogenetic abnormalities. Range from very good (0) to very poor (4)

  7. Safety as determined by frequency, nature and severity of adverse events [ Time Frame: 13 months ]
    Per CTCAE v4.0


Secondary Outcome Measures :
  1. Pharmacokinetic behavior of Nerofe: Maximum Plasma Concentration (Cmax) [ Time Frame: At cycles 1 and 2 (Cycle length 28 days) ]
    Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.

  2. Pharmacokinetic behavior of Nerofe: Minimum Plasma Concentration (Cmin) [ Time Frame: At cycles 1 and 2 (Cycle length 28 days) ]
    Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.

  3. Pharmacokinetic behavior of Nerofe: Area Under the Curve (AUC) [ Time Frame: At cycles 1 and 2 (Cycle length 28 days) ]
    Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.

  4. Pharmacokinetic behavior of Nerofe: Tmax [ Time Frame: At cycles 1 and 2 (Cycle length 28 days) ]
    Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.

  5. Pharmacodynamic analysis of changes from baseline in levels of circulating cytokines [ Time Frame: Every cycle (Cycle length 28 days) ]
    At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)

  6. Pharmacodynamic analysis of changes from baseline in levels of soluble T1/ST2 receptor [ Time Frame: Every cycle (Cycle length 28 days) ]
    At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)

  7. Pharmacodynamic analysis of changes from baseline in PBMCs' T1/ST2 receptor expression [ Time Frame: Every cycle (Cycle length 28 days) ]
    At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Males and females ≥18 years of age.
  2. 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.
  3. Anti-tumor (in this case the anti-MDS or anti-leukemic) effect can be measured according to the IWG criteria (Appendices B, C).
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  5. 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
  6. Negative serum β hCG test in women of childbearing potential
  7. Women of childbearing potential must agree to use dual contraceptive methods while on study drug and for 3 months afterward.
  8. Men who partner with a woman of childbearing potential must agree to use effective, dual contraceptive methods while on study drug and for 3 months afterward.
  9. Willing and able to provide written acceptance that during the trial, bone marrow examination should be performed, with cytogenetics. Bone marrow examination will be performed at Screening, Cycle 3, every odd subsequent cycles and End of Dosing Visit (as per PI and Medical Monitor decision).
  10. Bone marrow positive for ST2 receptor expression.
  11. Willing and able to provide written Informed Consent and comply with the requirements of the study

Exclusion Criteria

  1. 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.
  2. Erythroid stimulating agents are allowed until one day prior to treatment initiation with study drug.
  3. 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
  4. Receipt of >1 prior regimen of genotoxic therapy.
  5. Previous bone marrow transplantation.
  6. Life expectancy <12 weeks.
  7. RBC transfusions for at least 1 week and platelet transfusions for at least 3 days prior to study entry.
  8. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness (AIDS).
  9. Known active hepatitis B or C or other active liver disease
  10. Active infection requiring systemic therapy.
  11. 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.
  12. 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).
  13. Uncontrolled hypertension and change in treatment regimen within the last month prior to screening.
  14. Risk of syncope, in the judgment of the Principle Investigator, according to the patient's history of Syncope.
  15. History of ongoing cardiac dysrhythmias requiring drug treatment.
  16. Malignancies during the last yearexcept for skin non-melanomatous tumors and thyroid carcinomas..
  17. Any known severe multiple allergy or acute allergic reaction.
  18. Use of any investigational agents within 4 weeks or 5 half-lives of initiation of study drug.
  19. Pregnant or lactating women.
  20. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the investigator's opinion, would make the patient inappropriate for entry into this study.

    For combination therapy only:

  21. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) ≤ 55 % as measured by ECHO.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03059615


Contacts
Contact: Yoram Devary, Phd +972-50-2597032 ydevary@immunesk.com
Contact: Uzi Sandler, Prof. +972-54-7884444 sandler@g.jct.ac.il

Locations
Israel
Rabin Medical Center Recruiting
Petach Tikva, Israel, 4941492
Contact: Ofir Wolach, MD    972-3-5246826    ofirw@clalit.org.il   
Principal Investigator: Ofir Wolach, MD         
Kaplan Medical Center Not yet recruiting
Reẖovot, Israel, 76100
Contact: Kalman Filanovsky, MD    972-8-9441383    kalmanph@clalit.org.il   
Principal Investigator: Kalman Filanovsky, MD         
Sponsors and Collaborators
Immune System Key Ltd
Investigators
Study Director: Yoram Devary Immune System Key Ltd

Responsible Party: Immune System Key Ltd
ClinicalTrials.gov Identifier: NCT03059615     History of Changes
Other Study ID Numbers: ISK-N102
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: August 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action