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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04061239
Other study ID # PALOMA
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 19, 2019
Est. completion date September 2026

Study information

Verified date October 2023
Source GWT-TUD GmbH
Contact Arnold Schröder, Dr.
Phone +49 (0) 351 25933
Email arnold.schroeder@g-wt.de
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Allogeneic stem cell transplantation (alloHCT) is considered the only potentially curative treatment option for MDS patients and is therefore often considered the standard treatment for mainly higher-risk MDS patients up to the age of 75 years. One common approach to "bridge" higher-risk MDS from the time of diagnosis to transplantation is a treatment with hypomethylating agents such as azacitidine due to its anticipated low toxicity profile. Alternative strategies are intensive 7+3 chemotherapy with anthracycline and cytarabine or direct and immediate transplantation. By this strategy the time interval for donor search can be significantly prolonged leading to a higher proportion of success.Nevertheless, not every patient initially eligible for transplantation undergoes this procedure subsequently. A direct prospective comparison of different therapeutic approaches as outlined above versus CPX-351 prior to alloHCT has not been performed so far and is subject of the PALOMA trial. We hypothesize that CPX-351 will lead to higher and more durable response rates including a more favourable safety profile and long-term outcome compared to currently used conventional care regimens approaches prior to alloHCT.


Recruitment information / eligibility

Status Recruiting
Enrollment 150
Est. completion date September 2026
Est. primary completion date March 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: - 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. - Male patients must be willing to refrain from sperm donation for 6 months following the last dose of CPX-351 and must use adequate contraception throughout the entire study period and for 6 months following the last dose of CPX-351. - Combined oral contraceptive pills are not recommended. It is recommended that during the study two medically accepted methods of contraception (e.g. as hormonal contraceptive methods along with a condom) apply. Exclusion Criteria: - 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), CBFß-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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
CPX-351
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.
Daunorubicin
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.
Cytarabine
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.
Azacitidine
Azacitidine at 75mg/m² for 7 days. Patients should receive a minimum of 2 and up to 6 cycles.

Locations

Country Name City State
Austria Ordensklinikum Linz Elisabethinen GmbH Linz
Austria Uniklinikum Salzburg - Landeskrankenhaus Salzburg
Germany Universitätsklinikum Aachen Aachen
Germany Universitätsklinikum Augsburg Augsburg
Germany Charité - Universitätsmedizin Berlin Berlin
Germany Helios Klinikum Berlin-Buch GmbH Berlin
Germany Universitätsklinikum Bonn (UKB) Bonn
Germany Klinikum Chemnitz-gGmbH Chemnitz
Germany Universitätsklinikum Carl Gustav Carus Dresden Dresden
Germany Universitätsklinikum Düsseldorf Düsseldorf
Germany Universitätsklinikum Essen Essen
Germany Klinikum Frankfurt (Oder) GmbH Frankfurt
Germany Universitätsklinikum Frankfurt Frankfurt
Germany Universitätsklinikum Halle Halle
Germany Medizinische Hochschule Hannover Hannover
Germany Universitätsklinikum Heidelberg Heidelberg
Germany Universitätsklinikum Jena Jena
Germany Gemeinschaftsklinikum Mittelrhein gGmbH Koblenz
Germany Universitätsklinikum Köln Köln
Germany Universitätsklinikum Leipzig AöR Leipzig
Germany Universitätsmedizin Mannheim Mannheim
Germany Klinikum rechts der Isar der TU München München
Germany Universitätsklinikum Münster Münster
Germany Klinikum Nürnberg Nürnberg
Germany Universitätsmedizin Rostock Rostock
Germany Robert-Bosch-Krankenhaus Stuttgart Stuttgart
Germany Universitätsklinikum Tübingen Tübingen
Germany Universitätsklinikum Ulm Ulm

Sponsors (1)

Lead Sponsor Collaborator
GWT-TUD GmbH

Countries where clinical trial is conducted

Austria,  Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Response rate To compare best and overall response rate of CPX-351 vs. CCR according to AML-ELN and MDS-IWG criteria 2 years
Secondary Toxicity Assessment To compare the safety and tolerability of CPX-351 vs. CCR measured by NCI CTCAE v5.0 2 years
Secondary Proportion of patients proceeding to alloHCT To compare the effects of CPX-351 vs. CCR on the proportion of patients proceeding to alloHCT 2 years
Secondary Minimal residual disease To compare the effect of CPX-351 vs. CCR on minimal residual disease which will be assessed at all times of bone marrow puncture 2 years
Secondary Patient's quality of life To compare the effect of CPX-351 vs. CCR on the quality of life. It will be measured using the EORTC-QLQ30 questionnaire 2 years
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