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CPX-351 in Higher Risk Myelodysplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: CPX-351 in cohort A Drug: CPX-351 in cohort B Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
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
Official Title: CPX-351 in Higher Risk Myelodysplastic Syndromes: a Phase I/ II Study as First Line or After Hypomethylating-agents Failure
Actual Study Start Date : April 29, 2020
Estimated Primary Completion Date : October 1, 2022
Estimated Study Completion Date : October 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort A - First line treatment
Untreated patients
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.


Experimental: Cohort B - Hypomethylating failure
Patients in absence of response after hypomethylating agents treatment
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.





Primary Outcome Measures :
  1. Response rate (CR, CRi, PR) [ Time Frame: 28 to 42 days after induction ]
    Response to induction therapy


Secondary Outcome Measures :
  1. Overall response rate (CR, CRi, PR, HI) [ Time Frame: 28 to 42 days after induction ]
    Response to induction therapy

  2. Event free survival [ Time Frame: 42 months ]
    Event free survival

  3. Response duration [ Time Frame: 42 months ]
    Duration of the response to induction therapy

  4. Overall survival [ Time Frame: 42 months ]
    Overall survival

  5. Toxicity profile - Duration of cytopenias [ Time Frame: 42 months ]
    Duration of cytopenias

  6. Toxicity profile - life threatening or fatal cytopenias [ Time Frame: 42 months ]
    Number of life threatening or fatal cytopenias

  7. Toxicity profile - hospitalization [ Time Frame: 42 months ]
    Time spent in hospital for induction and consolidation cycles

  8. Evaluation of minimal residual disease (MRD) after induction and after the last consolidation [ Time Frame: 42 months ]
    Evaluation of MRD by flow cytometry

  9. 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

  10. 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



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT04273802


Contacts
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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

Locations
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France
CHU d'Amiens - Service d'hématologie clinique et thérapie cellulaire Not yet recruiting
Amiens, France, 80054
Contact: Bérengère GRUSON, MD    +33 3 22 45 59 14    gruson.berengere@chu-amiens.fr   
Principal Investigator: Bérengère GRUSON, MD         
Sub-Investigator: Amandine CHARBONNIER, MD         
Sub-Investigator: Magalie JORIS, MD         
CHU d'Angers - Service des maladies du sang Not yet recruiting
Angers, France, 49933
Contact: Sylvain THEPOT, MD    +33 2 41 35 44 66    sylvain.thepot@chu-angers.fr   
Principal Investigator: Sylvain THEPOT, MD         
Sub-Investigator: Corentin ORVAIN, MD         
Sub-Investigator: Aline SCHMIDT, MD         
CHU de Besançon - Hôpital Jean Minjoz - Service d'hématologie clinique Not yet recruiting
Besançon, France, 25030
Contact: Ana BERCEANU, MD    +33 3 81 66 83 51    aberceanu@chu-besancon.fr   
Principal Investigator: Ana BERCEANU, MD         
Sub-Investigator: Etienne DAGUINDAU, MD         
Sub-Investigator: Yohan DESBROSSES, MD         
CHU de Grenoble - Clinique universitaire d'hématologie Not yet recruiting
Grenoble, France, 38043
Contact: Sophie PARK, MD    +33 4 76 76 62 77    spark@chu-grenoble.fr   
Principal Investigator: Sophie PARK, MD         
Sub-Investigator: Anne THIEBAUT, MD         
Sub-Investigator: Frédéric GARBAN, MD         
CH Le Mans - Service d'onco-hématologie Not yet recruiting
Le Mans, France, 72037
Contact: Kamel LARIBI, MD    +33 2 43 43 43 61    klaribi@ch-lemans.fr   
Principal Investigator: Kamel LARIBI, MD         
Sub-Investigator: Nathalie DENIZON, MD         
Sub-Investigator: Anne BESANCON-BERGELIN, MD         
CHRU de Limoges - Hôpital Dupuytren - Service d'hématologie clinique et thérapie cellulaire Not yet recruiting
Limoges, France, 87042
Contact: Pascal TURLURE, MD    +33 5 55 05 66 42    pascal.turlure@chu-limoges.fr   
Principal Investigator: Pascal TURLURE, MD         
Sub-Investigator: Mohamed TOUATI, MD         
Sub-Investigator: Stéphane MOREAU, MD         
CHU Hôtel Dieu - Service d'Hématologie Clinique Recruiting
Nantes, France, 44093
Contact: Pierre PETERLIN, MD    +33 2 40 08 32 71    pierre.peterlin@chu-nantes.fr   
Principal Investigator: Pierre PETERLIN, MD         
Sub-Investigator: Patrice CHEVALLIER, MD         
Sub-Investigator: Thierry GUILLAUME, MD         
CHU-Hôpital Archet I - Service d'Hématologie Clinique Recruiting
Nice, France, 06202
Contact: Thomas CLUZEAU, MD    +33 4 92 03 58 44    cluzeau.t@chu-nice.fr   
Principal Investigator: Thomas CLUZEAU, MD         
Sub-Investigator: Michel LOSCHI, MD         
Sub-Investigator: Jean Michel KARSENTI, MD         
Hôpital Saint Louis - Service Hématologie Séniors Not yet recruiting
Paris, France, 75010
Contact: Pierre FENAUX, MD    +33 1 71 20 70 22    pierre.fenaux@aphp.fr   
Principal Investigator: Pierre FENAUX, MD         
Sub-Investigator: Marie SEBERT, MD         
Sub-Investigator: Lionel ADES, MD         
CHU de Bordeaux - Hôpital de Haut-Lévêque - Service des maladies du sang Not yet recruiting
Pessac, France, 33604
Contact: Sophie DIMICOLI-SALAZAR, MD    +33 5 57 65 65 11    sophie.dimicoli-salazar@chu-bordeaux.fr   
Principal Investigator: Sophie DIMICOLI-SALAZAR, MD         
Sub-Investigator: Arnaud PIGNEUX, MD         
Sub-Investigator: Axelle LASCAUX, MD         
CHU de Poitiers - Service d'onco-hématologie et thérapie cellulaire Not yet recruiting
Poitiers, France, 86021
Contact: Jose Miguel TORREGROSA DIAZ, MD    +33 5 48 44 44 44 ext 45415    jose-miguel.torregrosa-diaz@chu-poitiers.fr   
Principal Investigator: Jose Miguel TORREGROSA DIAZ, MD         
Sub-Investigator: Emilie CAYSSIALS, MD         
Sub-Investigator: Maria Pilar GALLEGO HERNANZ, MD         
IUCT-oncopole - Fédération Hématologie - Médecine Interne Not yet recruiting
Toulouse, France, 31059
Contact: Odile BEYNE-RAUZY, MD    +33 5 31 15 62 64    beynerauzy.odile@iuct-oncopole.fr   
Principal Investigator: Odile BEYNE-RAUZY, MD         
Sub-Investigator: Thibault COMONT, MD         
Sub-Investigator: Suzanne TAVITIAN, MD         
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Investigators
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Principal Investigator: Pierre PETERLIN, MD CHU Nantes
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Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT04273802    
Other Study ID Numbers: GFM-CPX-MDS
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: June 19, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Groupe Francophone des Myelodysplasies:
MDS high risk
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms