Comparison of Therapies Before Stem Cell Transplantation in Patients With Higher Risk MDS and Oligoblastic AML

NCT04061239 | Recruiting Phase 2

• 1 other identifier: PALOMA
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 28

Brief Summary

To compare the event-free survival at 2 years of CPX-351 vs. conventional care regimens before allogeneic blood cell transplantation as first line treatment in patients with higher risk MDS and oligoblastic AML.

Conditions

MDS; AML

Outcome Measures

Primary Outcomes (1)

• 2-year EFS in both arms

  To compare the event-free survival (EFS) at 2 years of CPX-351 vs. CCR before allogeneic blood cell transplantation (alloHCT) as first line treatment in patients with higher risk MDS and oligoblastic AML.

  2 years

Secondary Outcomes (5)

• Response rate

  2 years

• Toxicity Assessment

  2 years

• Proportion of patients proceeding to alloHCT

  2 years

• Minimal residual disease

  2 years

• Patient's quality of life

  2 years

Study Arms (2)

CPX-351 Arm

EXPERIMENTAL

CPX-351 is a liposomal formulation with a fixed 5:1 molar ratio of cytarabine and daunorubicin. It will be administered as a 90-minute intravenous infusion. The treatment includes up to 2 cycles of induction as follows: * 1 x CPX-351 1st induction: daunorubicin 44 mg/m² and cytarabine 100 mg/m² in liposomes on days 1, 3, and 5 * 1 x CPX-351 2nd induction: daunorubicin 44 mg/m² and cytarabine 100 mg/m² in liposomes on days 1 and 3 Each induction cycle will last 28 days. Depending on the type and extent of response as well as toxicity, the patient may continue on to consolidation therapy after induction or be discontinued from the treatment phase and transferred directly to alloHCT, if applicable. CPX-351 consolidation is with daunorubicin 29 mg/m² and cytarabine 65 mg/m² in liposomes on days 1 and 3. For patients \< 60 years up to 3 consolidation cycles and for patients ≥ 60 years up to 2 consolidation cycles are allowed.

Drug: CPX-351

CCR Arm

OTHER

The conventional care regimens (CCR) arm has 2 options according to the discretion of the investigator: 1. conventional "7+3" cytarabine/daunorubicin chemotherapy regimen 2. treatment with s.c. Azacitidine

Drug: Daunorubicin; Drug: Cytarabine; Drug: Azacitidine

Interventions

CPX-351 DRUG

CPX-351 is a liposomal formulation with a fixed 5:1 molar ratio of cytarabine and daunorubicin. It will be administered as a 90-minute intravenous infusion.

Also known as: Vyxeos

CPX-351 Arm

Daunorubicin DRUG

Daunorubicin is commercially available as a powder for reconstitution in 20 mg vials. In this trial, daunorubicin should be administered as an IV infusion over 60 min.

CCR Arm

Cytarabine DRUG

Cytarabine is commercially available as vials/bottles for preparation of diluted infusion solution. Cytarabine will be administrated intravenously. In this trial, cytarabine is administered as a continuous infusion.

CCR Arm

Azacitidine DRUG

Azacitidine at 75mg/m² for 7 days. Patients should receive a minimum of 2 and up to 6 cycles.

Also known as: Vidaza

CCR Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adult patients, 18-75 years of age
• Diagnosis of high risk MDS including oligoblastic non-proliferative (WBC \<13 Gpt/l) AML up to 29% of bone marrow blasts
• Availability of BM blast count from central morphology
• Bone marrow blasts ≥ 5%
• IPSS score intermediate or high
• alloHCT intended within the next 6 months
• ECOG performance status of 0 or 1
• Signed informed consent
• Laboratory values fulfilling the following:
• Serum creatinine \< 2.0 mg/dL
• Serum total bilirubin \< 2.0 mg/dL
• Serum alanine aminotransferase or aspartate aminotransferase \< 3 times the ULN
• Cardiac ejection fraction (LVEF) ≥ 50% by echocardiography
• Contraception:
• Female subjects of childbearing potential† must agree to use a medically acceptable method of contraception for at least 2 months prior to the first dose of CPX-351 and consent of female patients to use a medically acceptable method of contraception throughout the entire study period and for 6 months following the last dose of CPX-351. Medically acceptable methods of contraception that may be used by the patient include abstinence, diaphragm and spermicide, intrauterine device (IUD), condom and vaginal spermicide, hormonal contraceptives (patients must be stable on hormonal contraceptives for at least the prior 3 months), surgical sterilization, or post-menopausal (≥2 years of amenorrhea). Medically acceptable methods of contraception that may be used by the male partner of a female patient are condom and spermicide or vasectomy (\>6 months prior to Day-1) and are to be used throughout the entire study period and for 6 months following the last dose of CPX-351.

You may not qualify if:

• Patients with history of myeloproliferative neoplasms (MPN) (defined as a history of essential thrombocytosis or
• polycythemia vera, or idiopathic myelofibrosis prior to the diagnosis of AML) or combined MDS/MPN are not eligible.
• WHO-2016 defined AML entities: AML with t(15;17), PML-RARA; AML with t(8;21), RUNX1-RUNX1T1, AML with inv(16)/t(16;16), CBFβ-MYH11; AML with biallelic CEBPA mutation; AML with mutated FLT3 or NPM1.
• Clinical evidence of active CNS leukemia.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse within one year.
• Any major surgery or radiation therapy within four weeks prior screening.
• Patients with prior treatment of either CPX-351, hypomethylating agents, cytarabine or intensive chemotherapy for high-risk MDS or AML.
• Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
• Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
• Patients with myocardial impairment of any cause (e.g. cardiomyopathy, ischemic heart disease, significant valvular dysfunction, hypertensive heart disease, and congestive heart failure) resulting in heart failure by New York Heart Association Criteria (NYHA Class III or IV staging).
• Active or uncontrolled infection. Patients with an infection receiving treatment (antibiotic, antifungal or antiviral treatment) may be entered into the study but must be afebrile and hemodynamically stable for ≥72 hrs.
• Current evidence of invasive fungal infection (blood or tissue culture); patients with recent fungal infection must have a subsequent negative cultures to be eligible; known HIV (new testing not required) or evidence of active hepatitis B or C infection (with rising transaminase values).
• Hypersensitivity to cytarabine, daunorubicin or liposomal products.
• History of Wilson's disease or other copper-metabolism disorder.
• Female patients who are pregnant or lactating.

Sponsors & Collaborators

• GWT-TUD GmbH: lead

Study Sites (28)

Ordensklinikum Linz Elisabethinen GmbH

Linz, 4020, Austria

RECRUITING

Uniklinikum Salzburg - Landeskrankenhaus

Salzburg, 5020, Austria

WITHDRAWN

Universitätsklinikum Aachen

Aachen, 52074, Germany

RECRUITING

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, 12200, Germany

RECRUITING

Helios Klinikum Berlin-Buch GmbH

Berlin, 13125, Germany

RECRUITING

Universitätsklinikum Bonn (UKB)

Bonn, 53127, Germany

RECRUITING

Klinikum Chemnitz-gGmbH

Chemnitz, 09113, Germany

RECRUITING

Universitätsklinikum Köln

Cologne, 50937, Germany

RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universitätsklinikum Essen

Essen, 45122, Germany

RECRUITING

Klinikum Frankfurt (Oder) GmbH

Frankfurt, 15236, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Universitätsklinikum Halle

Halle, 06120, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, 30625, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum Jena

Jena, 07740, Germany

RECRUITING

Gemeinschaftsklinikum Mittelrhein gGmbH

Koblenz, 56068, Germany

RECRUITING

Universitätsklinikum Leipzig AöR

Leipzig, Germany

RECRUITING

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

RECRUITING

Klinikum rechts der Isar der TU München

München, 81675, Germany

RECRUITING

Universitätsklinikum Münster

Münster, 48149, Germany

RECRUITING

Klinikum Nürnberg

Nuremberg, 90419, Germany

RECRUITING

Universitätsmedizin Rostock

Rostock, 18055, Germany

RECRUITING

Robert-Bosch-Krankenhaus Stuttgart

Stuttgart, 70376, Germany

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

MeSH Terms

Interventions

CPX-351; Daunorubicin; Cytarabine; Azacitidine

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Ribonucleosides

Study Officials

• Uwe Platzbecker, Prof.

  Universitätsklinikum Leipzig AöR

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arnold Schröder, Dr.

CONTACT

+49 (0) 351 25933; arnold.schroeder@g-wt.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 19, 2019
• Study Start: August 19, 2019
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: October 11, 2023

Record last verified: 2023-10

Locations

DE (26); AU (2)