Study of NEROFE, a Novel Hormone-Peptide in Adult Patients With Advanced MDS and AML

NCT04365179 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 20190675
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label Phase 1b study of NEROFE following a traditional 3+3 design to assess safety and to determine the Recommended Phase 2 Dose (RP2D) of NEROFE in patients with MDS or AML. IV NEROFE will be administered three times per week on alternate days. The exact dosage will be determined using the body surface area (BSA) measured on Day 1 of each cycle.

Conditions

Advanced MDS; AML

Outcome Measures

Primary Outcomes (9)

• Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment for MDS patients

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

  At Screening (Day 1), at cycle 3 (Day 1) at cycle 5 (Day 1), at cycle 7 (Day 1), at cycle 9 (Day 1) at cycle 11 (Day 1) and at End of Treatment Visit. Cycle length is 28 days. Through study completion, an average of 1 year.

• Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment for MDS patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure hemoglobin (g/dL). Range 4-18 (4 worse outcome and 18 best outcome)

  At every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment 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 every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment 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 every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment for MDS patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure cytogenetic abnormalities. Range from very good (0) to very poor (4).

  At every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in ELN 2017 (European Leukemia Net) Criteria to evaluate response to Nerofe Treatment for AML patients

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

  At Screening (Day 1), at cycle 3 (Day 1) at cycle 5 (Day 1), at cycle 7 (Day 1), at cycle 9 (Day 1) at cycle 11 (Day 1) and at End of Treatment Visit. Cycle length is 28 days. Through study completion, an average of 1 year.

• Assessing change in ELN 2017 (European Leukemia Net) Criteria to evaluate response to Nerofe Treatment for AML 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 every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in ELN 2017 (European Leukemia Net) Criteria to evaluate response to Nerofe Treatment for AML patients. A calculation of several variables.

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

  At every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

• Assessing change in ELN 2017 (European Leukemia Net) Criteria to evaluate response to Nerofe Treatment for AML patients. A calculation of several variables.

  Complete Blood Count (CBC) to measure cytogenetic abnormalities. Range from very good (0) to very poor (4).

  At every cycle on Day 1, Day 3, Day 8, Day 10, Day 12, D15, Day 17, Day 19, Day 22, Day 24, Day 26 and Day 28 (cycle length is 28 days), and at End of Treatment Visit, through study completion, an average of 1 year.

Study Arms (1)

NEROFE

EXPERIMENTAL

Dose Level - Nerofe Dose -1 - 6mg/m2 1. \- 12 mg/m2 2. \- 24 mg/m2 3. \- 48 mg/m2 4. \- 96 mg/m2 5. \- 150mg/m2

Drug: Nerofe

Interventions

Nerofe DRUG

Up to 12 cycles of 28 days are planned. If patients are deriving benefit, treatment may continue past 12 cycles. Cycle 1: During Cycle 1, assigned NEROFE doses will be administered by intravenous (IV) infusion over 1 hour on Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26. Cycles 2-12: Subsequent cycles will be administered as above, presuming that patients do not meet criteria for study withdrawal during cycle 1.

NEROFE

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of one of the following:
• Relapsed/refractory Acute Myelogenous Leukemia (AML) where no alternative life prolonging therapy exists. Adverse genetic risk treatment naïve patients may also be considered eligible if, in the opinion of the investigator, these patients are unlikely to benefit from alternative therapy (e.g., an older patient with adverse risk MDS who progresses to AML after failing treatment for MDS (i.e. hypomethylating agent (HMA) or HMA and Venetoclax and is not a candidate for traditional AML induction chemotherapy).
• Relapsed/refractory Myelodysplastic Syndrome (MDS) those who fail to achieve a complete remission (CR) with at least 4 cycles of HMA (e.g. decitabine or azacitidine); or those who have progressive disease or have intolerance of HMA therapy after at least 2 cycles. Intolerance to HMA includes those patients forced to stop the HMA after at least 2 cycles due to severe infections/worsening cytopenias and are otherwise considered eligible. Patients with MDS have to have intermediate, high, or very high risk disease by International Prognostic Scoring System - Revised (IPSS-R score).
• Adult male or female patients 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Patients must satisfy the following laboratory criteria:
• Pre-treatment bone marrow staining must demonstrate expression of the ST2 receptor by IHC (low or high expression is allowed).
• Total bilirubin \< 1.5 x greater upper limit of normal (UNL). Elevated indirect bilirubin associated with post-transfusion hemolysis is allowed.
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be \< 3 x UNL
• Creatinine \< 2 x UNL or calculated creatinine clearance \> 40 ml/min; or Estimated Glomerular Filtration Rate (eGFR) \<50 according to MDRD (Modification of Diet in Renal Disease) method.
• White blood cell count (WBC) \< 25,000/uL before the administration of NEROFE on Cycle 1 Day 1. Use of hydroxyurea to control the level of circulating leukemic blast cell counts is allowed before and during the study.
• Suitable venous access to allow for all study related blood sampling (safety and research).
• Estimated life expectancy, in the judgment of the investigator, which will permit receipt of at least 8 weeks of treatment.
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without jeopardy to future medical care.
• Female patients who are:

You may not qualify if:

• Patients with a diagnosis of acute promyelocytic leukemia (APL).
• Screening bone marrow slide without staining for ST2 receptor. (Low or High expression by Immunohistochemistry \[IHC\] allowed on study).
• Therapy with any investigational products, anti-neoplastic therapy, or radiotherapy within 14 days of Cycle 1 Day 1. Patients actively receiving hydroxyurea are eligible and may continue to receive this medication during treatment on this protocol.
• Candidates for standard and/or potentially curative treatments. (A candidate is defined as a patient that is both eligible and willing to have these treatments.)
• Major surgery within 30 days of the first dose of any study drug or a scheduled surgery during study period.
• Grade 2 or higher diarrhea (as defined by NCI CTCAE Version 5.0) despite optimal anti-diarrheal supportive care within 7 days prior to Cycle 1 Day 1.
• Known cardiopulmonary disease as defined by one of the following:
• Clinically significant arrhythmia including: history of polymorphic ventricular fibrillation or torsade de pointes; atrial fibrillation \> 7 days and requiring cardioversion in the 4 weeks before screening; incompletely controlled, symptomatic atrial fibrillation. Patients with Afib are permitted to enroll if it is \< Grade 3 for a period of 6 months or greater and the rate is controlled with a stable regimen.
• Congestive heart failure (New York Heart Association (NYHA) Class III or IV; or Class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within four weeks of screening; myocardial infarction (MI) and/or revascularization (e.g.
• coronary bypass graft/stent) within 6 months of first dose of study drug.;
• Patients with ischemic heart disease who have had acute coronary syndrome (ACS), MI\< and/or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.
• Moderate to severe aortic and/or mitral valve stenosis or other ongoing valvulopathy;
• Pulmonary hypertension (symptomatic)
• Prolonged rate corrected QT (QTc) interval \>480 msec, calculated according to institutional guidelines;
• Known, active left ventricular ejection fraction (LVEF) \< 50% as assessed by echocardiogram or radionuclide angiography (not required at screening);

Sponsors & Collaborators

• Immune System Key Ltd: lead
• University of Miami Sylvester Comprehensive Cancer Center: collaborator

Study Sites (1)

University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Interventions

tumor-cells apoptosis factor, human

Central Study Contacts

Justin Watts, MD

CONTACT

305-243-3084; jxw401@miami.edu

Amber Thomassen, APRN-BC

CONTACT

305-243-7042; axt283@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: traditional 3+3 design

Study Record Dates

• First Submitted: April 12, 2020
• First Posted: April 28, 2020
• Study Start: June 18, 2020
• Primary Completion: June 30, 2025
• Study Completion: August 30, 2025
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)