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CPX-351 in Higher Risk Myelodysplastic Syndromes

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ClinicalTrials.gov Identifier: NCT04273802
Recruitment Status : Recruiting
First Posted : February 18, 2020
Last Update Posted : June 19, 2020
Sponsor:
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies

Tracking Information
First Submitted Date  ICMJE February 12, 2020
First Posted Date  ICMJE February 18, 2020
Last Update Posted Date June 19, 2020
Actual Study Start Date  ICMJE April 29, 2020
Estimated Primary Completion Date October 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
Response rate (CR, CRi, PR) [ Time Frame: 28 to 42 days after induction ]
Response to induction therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
  • Overall response rate (CR, CRi, PR, HI) [ Time Frame: 28 to 42 days after induction ]
    Response to induction therapy
  • Event free survival [ Time Frame: 42 months ]
    Event free survival
  • Response duration [ Time Frame: 42 months ]
    Duration of the response to induction therapy
  • Overall survival [ Time Frame: 42 months ]
    Overall survival
  • Toxicity profile - Duration of cytopenias [ Time Frame: 42 months ]
    Duration of cytopenias
  • Toxicity profile - life threatening or fatal cytopenias [ Time Frame: 42 months ]
    Number of life threatening or fatal cytopenias
  • Toxicity profile - hospitalization [ Time Frame: 42 months ]
    Time spent in hospital for induction and consolidation cycles
  • Evaluation of minimal residual disease (MRD) after induction and after the last consolidation [ Time Frame: 42 months ]
    Evaluation of MRD by flow cytometry
  • Evaluation of minimal residual disease (MRD) after induction and after the last consolidation [ Time Frame: 42 months ]
    Evaluation of variant allelic frequency (VAF) of Baseline mutations
  • Soluble Fms-like tyrosine kinase 3 ligand concentration (sFLc) in plasma during induction [ Time Frame: 42 months ]
    sFLc plasma level assessments at day 1 of induction just before starting treatment, and then at days 8, 15 and 22 of induction
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CPX-351 in Higher Risk Myelodysplastic Syndromes
Official Title  ICMJE CPX-351 in Higher Risk Myelodysplastic Syndromes: a Phase I/ II Study as First Line or After Hypomethylating-agents Failure
Brief Summary Study of the efficacy of CPX-351 treatment in patients with higher risk myelodysplastic syndromes : as first line treatment or after hypomethylating agents failure
Detailed Description

A phase I/II study of the efficacy of CPX-351 treatment in patients with higher risk myelodysplastic syndromes : as first line treatment or after hypomethylating agents failure.

CPX-351 is an advanced liposomal formulation of daunorubicin and cytarabine encapsulated at a 1:5 ratio.

Patients will receive induction treatment with CPX-351. Patients in response (complete response (CR), complete response with incomplete hematologic improvement (CRi), partial response (PR)) after induction will receive monthly courses of consolidation therapy with CPX-351.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Cohort A: first line treatment Cohort B: after hypomethylating-agents failure
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: CPX-351 in cohort A

    Treatment by CPX-351 via intravenous infusion over 90 minutes.

    Induction treatment with CPX-351 100 Units/m²/D on days 1, 3 and 5.

    If response after this induction treatment, 4 courses of consolidation therapy with CPX-351 100 Units/m²/D on day 1.

    If no response after this induction treatment, a second induction course of CPX-351 100 Units/m²/D on days 1 and 3. If response is achieved after this salvage course, 3 courses of consolidation therapy with CPX-351 100 Units/m²/D on day1.

  • Drug: CPX-351 in cohort B

    Treatment by CPX-351 via intravenous infusion over 90 minutes.

    This will be a dose-finding study : CPX-351 100 Units/m²/D on days 1, 3 and 5 or CPX-351 100 Units/m²/D on days 1 and 3 or CPX-351 60 Units/m²/D on days 1 and 3.

    In response after induction treatment, 4 monthly courses of consolidation therapy with CPX-351 at the same dose on day 1.

Study Arms  ICMJE
  • Experimental: Cohort A - First line treatment
    Untreated patients
    Intervention: Drug: CPX-351 in cohort A
  • Experimental: Cohort B - Hypomethylating failure
    Patients in absence of response after hypomethylating agents treatment
    Intervention: Drug: CPX-351 in cohort B
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2020)
65
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 1, 2023
Estimated Primary Completion Date October 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Myelodysplastic syndrome (WHO 2016 classified) including CMML (even if white blood cell count (WBC) > 13000/mm3).
  • For COHORT A: untreated patients except by erythropoiesis stimulating agents, Lenalidomide or non-chemotherapy during a phase of lower risk MDS; For COHORT B: absence of response (CR, CRi, PR or HI according to international working group (IWG) 2006 for MDS) after a minimum of 6 cycles of single hypomethylating agent or relapse after a response.
  • For COHORT A: less than 20% of marrow blasts. For COHORT B: less than doubling of marrow blasts compared with onset of hypomethylating agent.
  • Classical international prognostic scoring system (IPSS) int-2 or high risk score.
  • For COHORT A: age between 18 and 70 years; For COHORT B: age ≥ 18 years.
  • For COHORT A: Performance status (ECOG grading) ≤ 1; For COHORT B: Performance status ≤ 2.
  • Eligible for standard intensive chemotherapy.
  • Absence of concomitant severe cardiovascular disease which would make intensive chemotherapy impossible, i.e. arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease, reduced left ventricular function assessed by multigated acquisition (MUGA) scan or echocardiogram.
  • Patient must have adequate organ function as indicated by the following laboratory values: Renal: Serum creatinine < 2 mg/dl or calculated creatinine clearance ≥ 60 mL/min by MDRD (modification of the diet in renal disease) or CKD-EPI (chronic kidney disease epidemiology collaboration) equation for patients with creatinine levels > 1.5xULN ; Hepatic: Serum total bilirubin ≤ 2.5xULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels ≥ 2 mg/dL, aspartate aminotransferase (ALT) and alanine aminotransferase (ALT) ≤ 2.5xULN, Alkaline Phosphatase ≤ 5xULN (if > 2.5xULN, then liver fraction should be ≤ 2.5xULN).
  • Patients not known to be refractory to platelet transfusions.
  • Female subjects of child-bearing potential must agree to undergo medically supervised pregnancy test prior to starting study drug. The first pregnancy test will be performed at screening (within 7 days prior to first study drug administration), and on the day of the first study drug administration and confirmed negative prior to dosing and Day 1 before dosing all subsequent cycles. Female patient is not actively breastfeeding at the time of study entry.
  • Female patients are either post-menopausal, free from menses for > 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agree to abstain from becoming pregnant throughout the study, starting with Visit 1. Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study and for 6 months (females and males) following the last dose of CPX-351.
  • Male patients agree to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving CPX-351 and for 6 months post study.
  • Patients are available for regular blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.
  • Patients have the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.

Exclusion Criteria:

  • Active and uncontrolled infection.
  • Last dose of hypomethylating agent given more than 4 months before entering the trial.
  • Uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.
  • Current participation or participation in a study with an investigational compound or device within 30 days of initial dosing with study drug.
  • Known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
  • Clinically active hepatitis B or hepatitis C infection.
  • Known allergy or hypersensitivity to any component of CPX-351.
  • "Currently active" second malignancy, other than non-melanoma skin cancer and in situ carcinoma of the cervix.
  • Subjects with a history of Wilson's disease or other copper-related disorder.
  • Treatment with growth factors such as erythropoietin alfa (EPO) or granulocyte colony-stimulating factor (G-CSF) or cytotoxic and non-cytotoxic agents (including low dose oral chemotherapy with the exception of hydroxyurea) in the 30 days before inclusion.
  • Treatment with systemic steroids that has not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs.
  • Clinical evidence of central nervous system leukemia.
  • Pregnancy or breastfeeding during the projected duration of the study.
  • Absence of social security.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pierre PETERLIN, MD +33 2 40 08 74 18 pierre.peterlin@chu-nantes.fr
Contact: Fatiha CHERMAT +33 1 71 20 70 59 fatiha.chermat-ext@aphp.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04273802
Other Study ID Numbers  ICMJE GFM-CPX-MDS
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Groupe Francophone des Myelodysplasies
Study Sponsor  ICMJE Groupe Francophone des Myelodysplasies
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Pierre PETERLIN, MD CHU Nantes
PRS Account Groupe Francophone des Myelodysplasies
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP