Clinical trial • Phase III • Oncology
CYCLOPHOSPHAMIDE for Lymphoblastic lymphoma
Phase III trial of CYCLOPHOSPHAMIDE for Lymphoblastic lymphoma.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Lymphoblastic lymphoma
- Trial Stage
- Phase III
- Drug Modality
- Small molecule|Peptide/protein/enzyme
- Paediatric Trial
- Yes
Key dates
- Initial CTIS Submission Date
- 04-03-2024
- First CTIS Authorization Date
- 09-04-2024
Trial design
Randomised, randomisation r1: standard arm (sa) prednisone 60 mg/m²/day for 21 days plus a 9 day tapering versus experimental arm (ea) dexamethasone 10 mg/m²/day for 14 days without tapering. randomisation r2 (high-risk patients): standard treatment arm versus intensified treatment arm with 2 additional doses of peg-asparaginase during protocol ib and an intensified protocol m (one course hr-1' followed by one standard high-dose methotrexate course, then hr-2' and a second hd-mtx course).-controlled Phase III trial.
- Randomised
- Yes
- Comparator
- Randomisation R1: Standard arm (SA) prednisone 60 mg/m²/day for 21 days plus a 9 day tapering versus Experimental arm (EA) dexamethasone 10 mg/m²/day for 14 days without tapering. Randomisation R2 (high-risk patients): Standard treatment arm versus Intensified treatment arm with 2 additional doses of PEG-asparaginase during protocol Ib and an intensified protocol M (one course HR-1' followed by one standard high-dose methotrexate course, then HR-2' and a second HD-MTX course).
Eligibility
Recruits paediatric patients.
- Pregnancy Exclusion
- Evidence of pregnancy or lactation period
- Vulnerable Population
- Children and adolescents are included. Written informed consent is required from parents and from the patient when applicable (>14 years of age or according to local law and regulation). Age-specific information sheets and consent/assent forms are provided (multiple age bands and country-specific versions), and re-consent/legal competence procedures are included in country documents.
Inclusion criteria
- {"criterion_text":"- Newly diagnosed lymphoblastic lymphoma"}
- {"criterion_text":"- Age <18 years at diagnosis"}
- {"criterion_text":"- Patient enrolled in a participating center"}
- {"criterion_text":"- Written informed consent of patient (>14 years of age or according to local law and regulation) and parents to trial participation and transfer and processing of data"}
- {"criterion_text":"- Willingness of patients and the investigator/pathologist to provide adequate slides/blocks for reference (molecular)pathology and international pathology panel and/or fresh or fresh frozen samples for genetic risk group stratification if these samples are available after standard diagnostic procedures."}
Exclusion criteria
- {"criterion_text":"- Lymphoblastic lymphoma as secondary malignancy"}
- {"criterion_text":"- Non-lymphoma related relevant medical, psychiatric or social conditions incompatible with trial treatment including among others : - prior organ transplant - severe immunodeficiency - demyelinating Charcot-Marie Tooth syndrome - serious acute or chronic infections, such as HIV, VZV and tuberculosis - urinary tract infection, cystitis, urinary outflow obstruction, severe renal impairment (e.g. creatinine clearance less than 20 ml/min) - severe hepatic impairment (bilirubin >3 times ULN, transaminases >10 times ULN) - myocardial insufficiency, severe arrhythmias - ulcers of the oral cavity and known active gastrointestinal ulcer disease - known hypersensitivity to any IMP and to any excipient"}
- {"criterion_text":"- Steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis"}
- {"criterion_text":"- Vaccination with live vaccines within 2 weeks before start of protocol Treatment"}
- {"criterion_text":"- Treatment started according to another protocol or pre-treatment with cytostatic drugs (except INITIAL EMERGENCIES)"}
- {"criterion_text":"- Participation in another clinical trial that interferes with the protocol, except NHL-BFM Registry 2012 and trials with different endpoints, involving aspects of supportive treatment, which can run parallel to LBL 2018 without influencing the outcome of this trial (e.g. trials on antiemetics, antibiotics, strategies for psychosocial support)"}
- {"criterion_text":"- Evidence of pregnancy or lactation period"}
- {"criterion_text":"- Sexually active adolescents not willing to use highly effective contraceptive method (pearl index < 1) until 12 months after end of cytostatic therapy"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Primary endpoints of randomization 1: For the randomized question 1 the cumulative incidence of relapse with involvement of the CNS (CNS-relapse, pCICR) is the primary endpoint.","definition_or_measurement_approach":"Cumulative incidence of relapse involving the central nervous system (CNS-relapse); measured as incidence of CNS relapse events in randomized R1 arms (standard prednisone regimen vs dexamethasone substitution)."}
- {"endpoint_text":"- Primary endpoints of randomization 2: For the randomized question 2 the estimated probability of event-free survival (pEFS) is the primary endpoint.","definition_or_measurement_approach":"Estimated probability of event-free survival (pEFS) in high-risk patients comparing intensified treatment versus standard treatment (R2)."}
Recruitment
- Recruitment Window Months
- 128
- Consent Approach
- Parental consent is required for minors; patients may provide consent according to local law (explicitly: written informed consent of patient (>14 years of age or according to local law and regulation) and parents). Age-specific information sheets and ICFs/assent forms are provided for different age bands and languages (country-specific versions listed in documentation).
Sponsor
Primary sponsor
- Full Name
- Universitaetsklinikum Muenster AöR
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Germany
Contract research organisations
- Name
- Scientia CRO Sp. z o.o.
- Responsibilities
- CRO
Third parties
- {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"Universitaet Muenster","duties_or_roles":"","organisation_type":"Educational Institution"}
- {"country":"Austria","full_name":"St. Anna Childrens Cancer Research Institute GmbH","duties_or_roles":"Co-sponsor for Austria","organisation_type":"Pharmaceutical company"}
- {"country":"Sweden","full_name":"Sahlgrenska University Hospital-Vastra Gotalandsregionen","duties_or_roles":"Reference pathology for the Nordic Countries","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Italy","full_name":"Consorzio Per Valutazioni Biologiche E Farmacologiche","duties_or_roles":"TMF maintenance","organisation_type":"Pharmaceutical company"}
- {"country":"Belgium","full_name":"Universitair Ziekenhuis Gent","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Poland","full_name":"Scientia CRO Sp. z o.o.","duties_or_roles":"CRO","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"Medizinische Hochschule Hannover","duties_or_roles":"","organisation_type":"Educational Institution"}
- {"country":"Finland","full_name":"Turku University Hospital","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Slovakia","full_name":"Univerzita Pavla Jozefa Safarika V Kosiciach","duties_or_roles":"","organisation_type":"Educational Institution"}
- {"country":"Netherlands","full_name":"Julius Clinical International B.V.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"Poland","full_name":"Samodzielny Publiczny Zaklad Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego W Lodzi","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Germany","full_name":"Medizinische Hochschule Hannover (second entry)","duties_or_roles":"","organisation_type":"Educational Institution"}
Co-sponsors
- St. Anna Childrens Cancer Research Institute GmbH
Investigational products
- Investigational Product Name
- CYCLOPHOSPHAMIDE
- Active Substance
- CYCLOPHOSPHAMIDE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 1000 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 4000 mg/m2
- Investigational Product Name
- CYTARABINE
- Active Substance
- CYTARABINE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 4000 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 5800 mg/m2
- Investigational Product Name
- PREDNISOLONE
- Active Substance
- PREDNISOLONE
- Modality
- Small molecule
- Routes Of Administration
- INTRATHECAL USE
- Route
- Intrathecal / Oral/IV depending on regimen
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 10 mg
- Maximum Dose
- maxTotalDoseAmount: 240 mg
- Investigational Product Name
- VINCRISTINE
- Active Substance
- VINCRISTINE SULFATE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 2 mg
- Maximum Dose
- maxTotalDoseAmount: 20 mg
- Investigational Product Name
- METHOTREXATE
- Active Substance
- METHOTREXATE SODIUM
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 5 gm/m2
- Maximum Dose
- maxTotalDoseAmount: 20 gm/m2
- Investigational Product Name
- MERCAPTOPURINE
- Active Substance
- MERCAPTOPURINE
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 60 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 3080 mg/m2
- Investigational Product Name
- DEXAMETHASONE
- Active Substance
- DEXAMETHASONE ACETATE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE AND ORAL USE
- Route
- IV/Oral
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 20 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 576.25 mg/m2
- Investigational Product Name
- DOXORUBICIN
- Active Substance
- DOXORUBICIN HYDROCHLORIDE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 30 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 120 mg/m2
- Investigational Product Name
- DAUNORUBICIN
- Active Substance
- DAUNORUBICIN
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 30 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 150 mg/m2
- Investigational Product Name
- VINDESINE
- Active Substance
- VINDESINE SULFATE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 5 mg
- Maximum Dose
- maxTotalDoseAmount: 10 mg
- Investigational Product Name
- IFOSFAMIDE
- Active Substance
- IFOSFAMIDE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 1600 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 4000 mg/m2
- Investigational Product Name
- PEGASPARGASE
- Active Substance
- PEGASPARGASE
- Modality
- Peptide/protein/enzyme
- Routes Of Administration
- INTRAVENOUS USE
- Route
- Intravenous
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 3750 IU
- Maximum Dose
- maxTotalDoseAmount: 18750 IU
- Investigational Product Name
- TIOGUANINE
- Active Substance
- TIOGUANINE
- Modality
- Small molecule
- Routes Of Administration
- ORAL USE
- Route
- Oral
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 60 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 840 mg/m2
- Investigational Product Name
- PREDNISONE
- Active Substance
- PREDNISONE
- Modality
- Small molecule
- Routes Of Administration
- INTRAVENOUS USE AND ORAL USE
- Route
- IV/Oral
- Authorisation Status
- prodAuthStatus 2
- Dose Levels
- maxDailyDoseAmount: 60 mg/m2
- Maximum Dose
- maxTotalDoseAmount: 1837.5 mg/m2
- Combination Treatment
- Yes
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