Evaluation of CPX-351 Versus Conventional Care Regimens Prior to Allogeneic Hematopoietic Cell Transplantation in High-Risk MDS and Oligoblastic AML Patients
- Trial ID
- 2024-515375-35-00
- Protocol
- PALOMA
- Sponsor
- GWT-Tud GmbH
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the **event-free survival (EFS)** at 2 years between CPX-351 and conventional care regimens (CCR) prior to allogeneic blood cell transplantation (alloHCT) as a first-line treatment in patients with higher risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). This is clinically relevant as it aims to determine the efficacy of CPX-351 in prolonging the period without disease progression or relapse, which is crucial for improving patient outcomes in these high-risk conditions.
Secondary objectives include:
- Comparing the best and overall response rates of CPX-351 versus CCR.
- Evaluating the safety and tolerability of CPX-351 compared to CCR.
- Assessing the effects of CPX-351 versus CCR on the proportion of patients proceeding to alloHCT.
- Investigating the impact of CPX-351 versus CCR on minimal residual disease (MRD).
- Comparing the effect of CPX-351 versus CCR on patients' quality of life.
Participants
The clinical trial involves **adult patients** aged 18 to 75 years, irrespective of gender, diagnosed with higher risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML), who are eligible and intended for allogeneic hematopoietic cell transplantation (HCT) within the next six months. The study population includes both male and female subjects, with a focus on those who have not received prior treatment for these conditions. Participants are required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial does not specify the total number of participants, as the sponsor has not provided this information. Key lifestyle considerations include the use of medically acceptable contraception for female subjects of childbearing potential and male subjects, with specific guidelines on contraception and sperm donation throughout the study period and for six months following the last dose of CPX-351. Participants must meet specific laboratory criteria, including serum creatinine, bilirubin, and liver enzyme levels, and have a cardiac ejection fraction of at least 50% as determined by echocardiography. The trial population was selected based on these criteria to ensure the safety and efficacy of the treatment being studied.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **CPX-351** compared to conventional care regimens in patients with higher risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML) who are eligible for allogeneic hematopoietic cell transplantation (alloHCT) within the next six months. This is a randomized, controlled, and double-blind trial, with the primary objective of comparing the event-free survival (EFS) at two years between the two treatment arms. The trial is expected to conclude by March 31, 2026, with recruitment having commenced on April 1, 2019.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and laboratory values. Following randomization, participants will receive either CPX-351 or a comparator treatment. The trial includes multiple follow-up visits to monitor treatment response, adverse events, and overall health status. The end-of-study visit will assess the primary and secondary endpoints, including overall survival, response rates, and quality of life. The expected duration of participant involvement is up to 162 days, depending on the treatment arm and individual response.
Participants may be withdrawn from the study early if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it in the participant's best interest. The trial will adhere to rigorous ethical standards, ensuring informed consent and the safety of all participants throughout the study duration.
Treatment
The clinical trial involves the administration of several **antineoplastic** agents, each with specific pharmaceutical forms, dosages, and routes of administration. The primary experimental medication is **Vyxeos Liposomal 44 mg/100 mg powder for concentrate for solution for infusion**, which contains the active substances **cytarabine** and **daunorubicin**. This formulation is administered intravenously, with a maximum daily dose of 100 units and a total treatment period of 162 days. The product is specifically labeled for the study and is provided by Jazz Pharmaceuticals Ireland Ltd.
**Cytarabine** is utilized in two different formulations within the trial. The first is a concentrate for solution for infusion, and the second is a solution for infusion. Both forms are administered intravenously, with a maximum daily dose of 1500 mg/m² and a treatment period of up to 197 days. These formulations serve as comparator treatments in the study.
**Daunorubicin Hydrochloride** is provided as a powder for solution for injection or infusion. It is administered intravenously, with a maximum daily dose of 60 mg/m² and a treatment period of 57 days. This formulation is also used as a comparator in the trial.
**Azacitidine** is included in the trial as a powder for suspension for injection. It is administered subcutaneously, with a maximum daily dose of 75 mg/m² and a treatment period of 156 days. This agent is used as a comparator treatment in the study.
Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to compare the event-free survival at two years of the experimental treatment, CPX-351, against conventional care strategies in patients with higher-risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML) prior to allogeneic stem cell transplantation.
Efficacy
The efficacy of the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoint is the 2-year **event-free survival (EFS)** in both arms of the study. Secondary endpoints include the best and overall response rate according to AML-ELN and MDS-IWG criteria, toxicity as measured by NCI CTCAE v5.0, the proportion of patients proceeding to allogeneic hematopoietic cell transplantation (alloHCT), overall survival at 2 years, minimal residual disease (MRD) assessed at all times of bone marrow puncture, and quality of life as measured by EORTC-QLQ30 supplemented by information on self-assessed concomitant diseases and demographics upon inclusion and at the end of treatment (EOT), if applicable.
The trial aims to compare the efficacy of CPX-351 versus conventional care strategies before alloHCT in patients with higher risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). The efficacy parameters will be collected and analyzed at specified timepoints throughout the study duration, with a focus on the 2-year EFS as the primary measure of efficacy. The quality of life assessments will be conducted using the EORTC-QLQ30 tool, providing a comprehensive evaluation of patient-reported outcomes. The trial is designed to provide robust data on the efficacy of the treatment regimens in improving survival and quality of life in the target patient population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adult patients (irrespective of sex), 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
- Bone marrow blasts ≥ 5% (central morphology Düsseldorf)
- 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 all of 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; 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
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), PMLRARA; AML with t(8;21), RUNX1-RUNX1T1, AML with inv(16)/t(16;16), CBFβ-MYH11; AML with BCR-ABL1, AML with biallelic CEBPA mutation; AML with mutated FLT3 or NPM1.
- Clinical evidence of active CNS leukaemia.
- 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 more than 2 years ago and are disease free.
- 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).
- Recent (< 30 days) or planned live vaccinations during the clinical trial.
- Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
- Creatinine clearance < 30 ml/min.
- 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, unless the therapy outweighs the risks.
- Female patients who are pregnant or lactating.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Not Recruiting | 01 Apr 2019 | 20 |
 Germany | Not Recruiting | 01 Apr 2019 | 130 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AZACITIDINE | Comparator | — | SUBCUTANEOUS USE | 75 | 156 | SUB05624MIG |
DAUNORUBICIN HYDROCHLORIDE | Comparator | — | INTRAVENOUS | 60 | 57 | SUB01556MIG |
CYTARABINE | Comparator | — | INTRAVENOUS | 1500 | 197 | SUB06880MIG |
AZACITIDINE | Comparator | — | SUBCUTANEOUS INJECTION | 75 | 156 | SUB05624MIG |
DAUNORUBICIN HYDROCHLORIDE | Comparator | — | INTRAVENOUS | 60 | 57 | SUB01556MIG |
CYTARABINE | Comparator | — | INTRAVENOUS | 1500 | 197 | SUB06880MIG |
Vyxeos Liposomal 44 mg/100 mg powder for concentrate for solution for infusion. | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 100 | 162 | PRD6605639 |