Primary comparison of therapies before stem cell transplantation in patients with higher risk MDS and oligoblastic AM

Phase 1

• Conditions: ntreated patients with higher risk MDS and oligoblastic AML eligible and intended for allogeneic HCT within the next 6 months; MedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002430-21-AT
• Lead Sponsor: GWT-TUD GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-04-02
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Adult patients, 18-75 years of age
2. Diagnosis of high risk MDS including oligoblastic non-proliferative (WBC <13 Gpt/l) AML up to 29% of bone marrow blasts
3. Bone marrow blasts = 5% (central morphology Düsseldorf)
4. IPSS score intermediate-2 or high
5. alloHCT intended within the next 6 months
6. ECOG performance status of 0 or 1
7. Signed informed consent
8. 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
9. Cardiac ejection fraction (LVEF) = 50% by echocardiography
10. Contraception:
- Female subjects of childbearing potential† must agree to use a medically acceptable method of contraception from signature of ICF (for at least 1 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 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.

†A female subject or a female partner of a male subject is considered to have childbearing potential unless she meets at least one of the following criteria: Age =50 years and naturally amenorrhoeic for = 1 year (amenorrhoea following cancer therapy does not rule out childbearing potential), premature ovarian failure confirmed by a specialist gynecologist, previous bilateral salpingo-oophorectomy or hysterectomy, XY genotype, Turner syndrome or uterine agenesis.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. 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.
2. 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 BCR-ABL1, AML with biallelic CEBPA mutation, AML with mutated FLT3 or NPM1.
3. Clinical evidence of active CNS leukaemia (assessment of CSF is not mandatory for screening).
4. 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.
5. Any major surgery or radiation therapy within four weeks prior screening.
6. Patients with prior treatment of either CPX-351, hypomethylating agents, cytarabine or intensive chemotherapy for high-risk MDS or AML.
7. Patients with prior cumulative anthracycline exposure of greater than 368 mg/m2 daunorubicin (or equivalent).
8. Recent (<30 days) or planned live vaccinations during the clinical trial
9. Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent obtaining informed consent.
10. Creatinine clearance < 30 ml/min
11. 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.
12. 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).
13. Hypersensitivity to cytarabine, daunorubicin or liposomal products.
14. History of Wilson’s disease or other copper-metabolism disorder, unless the therapy outweighs the risks.
15. Female patients who are pregnant or lactating.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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.;Secondary Objective: • To compare best and overall response of CPX-351 vs. CCR<br>• To compare the safety and tolerability of CPX-351 vs. CCR<br>• To compare the effects of CPX-351 vs. CCR on the proportion of patients proceeding to alloHCT<br>• To compare the effect of CPX-351 vs. CCR on minimal residual disease (MRD)<br>• To compare the effect of CPX-351 vs. CCR on quality of life;Primary end point(s): 2-year EFS in both arms;Timepoint(s) of evaluation of this end point: After LPLV (EOS)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Best and overall response rate according to AML-ELN and MDS-IWG criteria<br>• Toxicity as measured by NCI CTCAE v5.0<br>• Proportion of patients proceeding to alloHCT<br>• Overall survival at 2 years<br>• MRD assessed at all times of BM puncture<br>• Quality of life as measured by EORTC-QLQ30 supplemented by information on self-assessed concomitant diseases and demographics upon inclusion and at EOT (i.e. before alloHCT, if applicable);Timepoint(s) of evaluation of this end point: After LPLV (EOS)