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Advanced MDSPhase 1NCT04365179

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

A Phase 1 study testing Nerofe in people with Advanced MDS and AML, run by Immune System Key Ltd at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced MDS, AML
What is being tested?
Nerofe
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
18 Jun 2020to 30 Aug 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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:
  • Postmenopausal for at least one year before the screening visit, OR
  • Surgically sterile, OR
  • If they are of childbearing potential:
  • Agree to practice one highly effective method and one additional effective (barrier) method of contraception, at the same time, form the time of signing the informed consent through 4 months after the last does of study drug (female and male condoms should not be used together), OR Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods; withdrawal; spermicides only; and lactational amenorrhea are not acceptable methods of contraception).
  • Male patients even if surgically sterilized (e.g. status post vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through four months after the last dose of study drug (female and male condoms should not be used together), OR
  • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence e.g. calendar, ovulation, symptothermal, postovulation methods; withdrawal; spermicides only; and lactational amenorrhea are not acceptable methods of contraception).
  • Able to undergo bone marrow examination at screening

Who cannot join

  • 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.
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  • 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);
  • Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease and/or pulmonary fibrosis (e.g., requiring home O2 therapy).
  • Active and uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia (stable or resolving infection on antibiotics is allowed).
  • Known human immunodeficiency virus (HIV) seropositive.
  • Known Hepatitis B surface antigen seropositive (note: patients who have isolated positive hepatitis B core antibody [e.g. in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody] must have an undetectable hepatitis viral load).
  • Known or suspected active hepatitis C infection. Patients with treated Hep C treated with a negative viral load are eligible.
  • Females of child bearing potential who refuse to practice two effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing consent through four months after the last dose of study drug.
  • Males of child bearing potential who refuse to practice effective barrier methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing consent through four months after the last dose of study drug.
  • Female patients who are both lactating or breastfeeding, or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.
  • Female patients who intend to donate eggs (ova) during the course of this study or within four months after receiving their last dose of study drug.
  • Male patients who intend to donate sperm during the course of this study or within four months after receiving their last dose of study drug.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of study procedures.
  • Symptomatic central nervous system (CNS) involvement.
  • Diagnosed or treated for another malignancy within 2 years with evidence of residual disease.
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment.
  • Patients with uncontrolled coagulopathy or bleeding disorder.
  • Use of systemic steroids (prednisone) >10mg/day or any equivalent corticosteroids within 7 days of Cycle 1 Day 1. Patients on other immunosuppression (such as post-transplant) and also ineligible. Patients with active, uncontrolled GVHD (Graft Versus Host Disease) are also ineligible. Otherwise patients are eligible post-bone marrow transplantation.
  • Life-threatening illnesses unrelated to cancer.

Trial locations and contacts

1 site in 1 country.

Justin Watts, MD contact

305-243-3084

jxw401@miami.edu

Amber Thomassen, APRN-BC contact

305-243-7042

axt283@miami.edu

United States1 site, 1 recruiting

  • University of Miami Hospital and Clinics / Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

    Justin M Watts, MD, 305-243-3084, jxw401@miami.edu

    Amber Thomassen, RN, 305 243 7042, axt283@miami.edu

    Recruiting

Other trials in United States

About this study

Official title: An Open-Label Phase 1b Study of NEROFE, a Novel Hormone-Peptide in Adult Patients With Advanced Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)

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.

Read the detailed description

NEROFE monotherapy may be administered for a maximum of 12 cycles provided that the patient tolerates treatment and there is evidence of clinical benefit. If patients are receiving clinical benefit, they may continue past 12 cycles.

Patients will be followed for a minimum of 30 days after the last dose of NEROFE monotherapy.

After this 30 day period, patients will only be followed for the resolution of any ongoing adverse events.

Conditions
Advanced MDS, AML
Being tested
Nerofe

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NerofeDrug

    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.

Study groups in NCT04365179
Study groupRoleWhat they receive
NEROFEExperimentalDose 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
Receives: Drug: Nerofe

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: 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.

  2. 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)

    Measured: 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.

  3. 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).

    Measured: 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.

  4. 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).

    Measured: 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.

  5. 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).

    Measured: 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.

  6. 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)

    Measured: 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.

  7. 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)

    Measured: 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.

  8. 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).

    Measured: 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.

  9. 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).

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2020
  2. Study start18 Jun 2020
  3. Primary completion30 Jun 2025 (estimated)
  4. Study completion30 Aug 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
traditional 3+3 design
Masking
None (open label)
Enrolment
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04365179
Sponsor's protocol ID
20190675
Status last verified
Jul 2024
First submitted
12 Apr 2020
Last updated
10 Jul 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nerofe in people with Advanced MDS and AML, run by Immune System Key Ltd at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Justin Watts, MD (305-243-3084, jxw401@miami.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessing change in IWG (International Working Group) Criteria to evaluate response to Nerofe Treatment for MDS patients (time frame: 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.). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04365179.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.

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