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Myelodysplastic SyndromesPhase 1/2NCT04273802

CPX-351 in Higher Risk Myelodysplastic Syndromes

A Phase 1/2 study testing CPX-351 in cohort A and CPX-351 in cohort B in people with Myelodysplastic Syndromes, run by Groupe Francophone des Myelodysplasies at 16 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
CPX-351 in cohort A and CPX-351 in cohort B
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
16 sitesFrance
Study dates
29 Apr 2020to 6 Jul 2022
Phase
Phase 1/2
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 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 and B : age between 18 and 70 years
  • For COHORT A: Performance status (ECOG grading) ≤ 1; For COHORT B: Performance status ≤ 2.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

France16 sites

  • CHU d'Amiens - Service d'hématologie clinique et thérapie cellulaire

    Amiens, 80054

  • CHU d'Angers - Service des maladies du sang

    Angers, 49933

  • Centre hospitalier Victor Dupouy - Service d'Hématologie

    Argenteuil, 95107

  • CHU de Besançon - Hôpital Jean Minjoz - Service d'hématologie clinique

    Besançon, 25030

  • CHU de Grenoble - Clinique universitaire d'hématologie

    Grenoble, 38043

  • CH Le Mans - Service d'onco-hématologie

    Le Mans, 72037

  • CHRU de Limoges - Hôpital Dupuytren - Service d'hématologie clinique et thérapie cellulaire

    Limoges, 87042

  • Institut Paoli Calmettes - Unité d'hématologie 3

    Marseille, 13273

  • CHU Hôtel Dieu - Service d'Hématologie Clinique

    Nantes, 44093

  • CHU-Hôpital Archet I - Service d'Hématologie Clinique

    Nice, 06202

  • Hôpital Saint Louis - Service Hématologie Séniors

    Paris, 75010

  • CHU de Bordeaux - Hôpital de Haut-Lévêque - Service des maladies du sang

    Pessac, 33604

  • CHU de Poitiers - Service d'onco-hématologie et thérapie cellulaire

    Poitiers, 86021

  • Hôpital Pontchaillou - Service d'hématologie clinique

    Rennes, 35033

  • Institut de Cancérologie Lucien Neuwirth - Hématologie Clinique - Thérapie Cellulaire

    Saint-Priest-en-Jarez, 42270

  • IUCT-oncopole - Fédération Hématologie - Médecine Interne

    Toulouse, 31059

Other trials in France

About this study

Official title: CPX-351 in Higher Risk Myelodysplastic Syndromes: a Phase I/ II Study as First Line or After Hypomethylating-agents Failure

Study of the efficacy of CPX-351 treatment in patients with higher risk myelodysplastic syndromes : as first line treatment or after hypomethylating agents failure

Read the 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.

Being tested
CPX-351 in cohort A, CPX-351 in cohort B
Keywords
MDS high risk
Medical subject headings
Myelodysplastic Syndromes

What participants receive

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

  • CPX-351 in cohort ADrug

    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.

  • CPX-351 in cohort BDrug

    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 groups in NCT04273802
Study groupRoleWhat they receive
Cohort A - First line treatmentExperimentalUntreated patients
Receives: Drug: CPX-351 in cohort A
Cohort B - Hypomethylating failureExperimentalPatients in absence of response after hypomethylating agents treatment
Receives: Drug: CPX-351 in cohort B

What is being measured

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

  1. Response rate (CR, CRi, PR)

    Response to induction therapy

    Measured: 28 to 42 days after induction

Secondary outcomes (10)

  1. Overall response rate (CR, CRi, PR, HI)

    Response to induction therapy

    Measured: 28 to 42 days after induction

  2. Event free survival

    Event free survival

    Measured: 42 months

  3. Response duration

    Duration of the response to induction therapy

    Measured: 42 months

  4. Overall survival

    Overall survival

    Measured: 42 months

  5. Toxicity profile - Duration of cytopenias

    Duration of cytopenias

    Measured: 42 months

  6. Toxicity profile - life threatening or fatal cytopenias

    Number of life threatening or fatal cytopenias

    Measured: 42 months

  7. Toxicity profile - hospitalization

    Time spent in hospital for induction and consolidation cycles

    Measured: 42 months

  8. Evaluation of minimal residual disease (MRD) after induction and after the last consolidation

    Evaluation of MRD by flow cytometry

    Measured: 42 months

  9. Evaluation of minimal residual disease (MRD) after induction and after the last consolidation

    Evaluation of variant allelic frequency (VAF) of Baseline mutations

    Measured: 42 months

  10. Soluble Fms-like tyrosine kinase 3 ligand concentration (sFLc) in plasma during induction

    sFLc plasma level assessments at day 1 of induction just before starting treatment, and then at days 8, 15 and 22 of induction

    Measured: 42 months

Timeline

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

  1. First posted18 Feb 2020
  2. Study start29 Apr 2020
  3. Primary completion27 Aug 2021
  4. Study completion6 Jul 2022

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Cohort A: first line treatment Cohort B: after hypomethylating-agents failure
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04273802
Sponsor's protocol ID
GFM-CPX-MDS
Status last verified
Jul 2022
First submitted
12 Feb 2020
Last updated
7 Jul 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Peterlin P, Le Bris Y, Turlure P, Chevallier P, Menard A, Gourin MP, Dumas PY, Thepot S, Berceanu A, Park S, Hospital MA, Cluzeau T, Bouzy S, Torregrosa-Diaz JM, Drevon L, Sapena R, Chermat F, Ades L, Dimicoli-Salazar S, Chevret S, Bene MC, Fenaux P. CPX-351 in higher risk myelodysplastic syndrome and chronic myelomonocytic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Haematol. 2023 Jul;10(7):e521-e529. doi: 10.1016/S2352-3026(23)00090-X. Epub 2023 May 25.

    PubMed 37245522

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CPX-351 in cohort A and CPX-351 in cohort B in people with Myelodysplastic Syndromes, run by Groupe Francophone des Myelodysplasies at 16 sites in France.

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 15 inclusion and 14 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: finished, as of the sponsor's last update on 7 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate (CR, CRi, PR) (time frame: 28 to 42 days after induction). 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 NCT04273802, which also lists 1 linked publication.

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 7 Jul 2022.

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