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

AML Clinical Trial

— PALOMA  

Official title:

Primary Comparison of Liposomal Anthracycline Based Treatment Versus Conventional Care Strategies Before Allogeneic Stem Cell Transplantation in Patients With Higher Risk MDS and Oligoblastic AML

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04061239
• Other study ID #: PALOMA
• Status: Recruiting
• Phase: Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• AML
• MDS

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