CPX-351 in Higher Risk Myelodysplastic Syndromes

NCT ID: NCT04273802

Last Updated: 2022-07-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-04-29

Study Completion Date

2022-07-06

Brief Summary

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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

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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.

Conditions

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Myelodysplastic Syndromes

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Cohort A: first line treatment Cohort B: after hypomethylating-agents failure
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A - First line treatment

Untreated patients

Group Type EXPERIMENTAL

CPX-351 in cohort A

Intervention Type DRUG

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.

Cohort B - Hypomethylating failure

Patients in absence of response after hypomethylating agents treatment

Group Type EXPERIMENTAL

CPX-351 in cohort B

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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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 and B : age between 18 and 70 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pierre PETERLIN, MD

Role: PRINCIPAL_INVESTIGATOR

Nantes University Hospital

Locations

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

Amiens, , France

Site Status

CHU d'Angers - Service des maladies du sang

Angers, , France

Site Status

Centre hospitalier Victor Dupouy - Service d'Hématologie

Argenteuil, , France

Site Status

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

Besançon, , France

Site Status

CHU de Grenoble - Clinique universitaire d'hématologie

Grenoble, , France

Site Status

CH Le Mans - Service d'onco-hématologie

Le Mans, , France

Site Status

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

Limoges, , France

Site Status

Institut Paoli Calmettes - Unité d'hématologie 3

Marseille, , France

Site Status

CHU Hôtel Dieu - Service d'Hématologie Clinique

Nantes, , France

Site Status

CHU-Hôpital Archet I - Service d'Hématologie Clinique

Nice, , France

Site Status

Hôpital Saint Louis - Service Hématologie Séniors

Paris, , France

Site Status

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

Pessac, , France

Site Status

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

Poitiers, , France

Site Status

Hôpital Pontchaillou - Service d'hématologie clinique

Rennes, , France

Site Status

Institut de Cancérologie Lucien Neuwirth - Hématologie Clinique - Thérapie Cellulaire

Saint-Priest-en-Jarez, , France

Site Status

IUCT-oncopole - Fédération Hématologie - Médecine Interne

Toulouse, , France

Site Status

Countries

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France

References

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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.

Reference Type DERIVED
PMID: 37245522 (View on PubMed)

Other Identifiers

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GFM-CPX-MDS

Identifier Type: -

Identifier Source: org_study_id

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