CPX-351 in Higher Risk Myelodysplastic Syndromes

NCT04273802 | Completed Phase 1 DMC

• 1 other identifier: GFM-CPX-MDS
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 16

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

Conditions

Myelodysplastic Syndromes

Keywords

MDS high risk

Outcome Measures

Primary Outcomes (1)

• Response rate (CR, CRi, PR)

  Response to induction therapy

  28 to 42 days after induction

Secondary Outcomes (10)

• Overall response rate (CR, CRi, PR, HI)

  28 to 42 days after induction

• Event free survival

  42 months

• Response duration

  42 months

• Overall survival

  42 months

• Toxicity profile - Duration of cytopenias

  42 months

Study Arms (2)

Cohort A - First line treatment

EXPERIMENTAL

Untreated patients

Drug: CPX-351 in cohort A

Cohort B - Hypomethylating failure

EXPERIMENTAL

Patients in absence of response after hypomethylating agents treatment

Drug: CPX-351 in cohort B

Interventions

CPX-351 in cohort A 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 A - First line treatment

CPX-351 in cohort B 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.

Cohort B - Hypomethylating failure

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead

Study Sites (16)

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

Amiens, 80054, France

Location

CHU d'Angers - Service des maladies du sang

Angers, 49933, France

Location

Centre hospitalier Victor Dupouy - Service d'Hématologie

Argenteuil, 95107, France

Location

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

Besançon, 25030, France

Location

CHU de Grenoble - Clinique universitaire d'hématologie

Grenoble, 38043, France

Location

CH Le Mans - Service d'onco-hématologie

Le Mans, 72037, France

Location

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

Limoges, 87042, France

Location

Institut Paoli Calmettes - Unité d'hématologie 3

Marseille, 13273, France

Location

CHU Hôtel Dieu - Service d'Hématologie Clinique

Nantes, 44093, France

Location

CHU-Hôpital Archet I - Service d'Hématologie Clinique

Nice, 06202, France

Location

Hôpital Saint Louis - Service Hématologie Séniors

Paris, 75010, France

Location

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

Pessac, 33604, France

Location

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

Poitiers, 86021, France

Location

Hôpital Pontchaillou - Service d'hématologie clinique

Rennes, 35033, France

Location

Institut de Cancérologie Lucien Neuwirth - Hématologie Clinique - Thérapie Cellulaire

Saint-Priest-en-Jarez, 42270, France

Location

IUCT-oncopole - Fédération Hématologie - Médecine Interne

Toulouse, 31059, France

Location

Related Publications (1)

• 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.

  PMID: 37245522 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Pierre PETERLIN, MD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort A: first line treatment Cohort B: after hypomethylating-agents failure

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 18, 2020
• Study Start: April 29, 2020
• Primary Completion: August 27, 2021
• Study Completion: July 6, 2022
• Last Updated: July 7, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)