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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
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.
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.
Rabin Medical Center
Petah Tikva, Israel
Kaplan Medical Center
Rehovot, Israel
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
Time frame: 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).
Time frame: 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).
Time frame: 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).
Time frame: 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)
Time frame: At end of Cycles 2, 4, 6, 8, 10, 12 (Cycle length 28 Days)
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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)
Time frame: 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
Time frame: 13 months
Pharmacokinetic behavior of Nerofe: Maximum Plasma Concentration (Cmax)
Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.
Time frame: At cycles 1 and 2 (Cycle length 28 days)
Pharmacokinetic behavior of Nerofe: Minimum Plasma Concentration (Cmin)
Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.
Time frame: At cycles 1 and 2 (Cycle length 28 days)
Pharmacokinetic behavior of Nerofe: Area Under the Curve (AUC)
Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.
Time frame: At cycles 1 and 2 (Cycle length 28 days)
Pharmacokinetic behavior of Nerofe: Tmax
Done at Cycle 1 and 2: pre-dose, 15 minutes, 1, 2, 4, 6, 8 and 24 hours.
Time frame: At cycles 1 and 2 (Cycle length 28 days)
Pharmacodynamic analysis of changes from baseline in levels of circulating cytokines
At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)
Time frame: Every cycle (Cycle length 28 days)
Pharmacodynamic analysis of changes from baseline in levels of soluble T1/ST2 receptor
At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)
Time frame: Every cycle (Cycle length 28 days)
Pharmacodynamic analysis of changes from baseline in PBMCs' T1/ST2 receptor expression
At Cycle 1 and 2 on Day 1 and Day 15 and on day 1 of each consecutive cycle (up to 12 cycles)
Time frame: Every cycle (Cycle length 28 days)