ASTRAL- a Clinical Study to Assess the Efficacy and Toxicity of High-dose Chemotherapy

This is a clinical study to assess the treatment (efficacy and toxicity) with a high dosed chemotherapy followed by stem cell transplantation in patients suffering from primary progressive and relapsed aggressive Non-Hodgkin Lymphoma (NHL)

After end of the active study phase, patients will receive further standard medical care at the discretion of the treating physician. The clinical consultants will provide advice on further treatment if requested.

Inclusion criteria

Subjects must fulfill all of the following criteria to be included in this trial:

• Provision of written informed consent and specifically the consent to the collection and processing of health-related data
• Age: 18 years and older
• Gender: Male and female patients
• Histology
• Diagnosis of relapsed or primary progressive aggressive B- or T-cell lymphoma including:

• B-Cell non-hodgkin lymphoma (B-NHL) or
• T-Cell non-hodgkin lymphoma (T-NHL):
• Staging at relapse or progression (data should not be older than 4 weeks):
• Staging after 2 or 3 cycles of salvage treatment:
• Donor availability:
• Females of childbearing potential (FCBP) must:

• Understand the potential teratogenic risk to the unborn child
• Understand the need and agree to utilize two reliable forms of contraception
• Understand and agree to inform the investigator if a change or stop of method of contraception is needed
• Be capable of complying with effective contraceptive measures
• Be informed and understand the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy
• Understand the need to commence the study treatment as soon as study drug is dispensed following a negative pregnancy test
• Understand the need and accept to undergo pregnancy testing based on the frequency outlined in this protocol
• Agree to abstain from breastfeeding during study participation
• Males must:

• Agree to use a latex condom during any sexual contact with females of childbearing potential
• Agree to refrain from donating semen or sperm while on the study drugs and should seek for sperm cryopreservation before therapy is started and should not father a child while treated and during one year after end of study treatment
• Females of non-childbearing potential:

Exclusion criteria

Subjects are to be excluded from the study if they display any of the following criteria:

• Pregnant females; lactating women must end breast feeding before start of study treatment
• Serious accompanying disorder or impaired organ function
• Central nervous system (CNS) involvement of lymphoma - to be examined in case of clinical symptoms
• History of severe cardiac diseases, and cardiac function impairment
• Severe kidney disease
• HIV-positivity
• Hepatitis B and C as defined by seropositivity
• Patients under legal guardianship regarding medical decisions
• Ongoing treatment or study procedures within any other clinical trial with the exception of follow up
• Ongoing exclusion periods of other clinical studies after end of treatment
• In patients tested: Metabolic Computer tomography (CR) in a positron emission tomography-Computer tomography (PET-CT) scan after the last cycle of therapy prior to planned SCT
• Subjects with known hypersensitivity to the study drugs
• Criteria which in the opinion of the investigator precluded participation for scientific reasons, for reasons of compliance, or for reasons of the subject's safety
• Commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities
• Dependency on the sponsor, trial site or investigator
• Additional exclusion criteria with respect to summary of product characteristics (SmPC) of the investigational medical product (IMPs) fludarabine, thiotepa, cyclophosphamide:

• Known hypersensitivity to fludarabine, thiotepa, cyclophosphamide or one of their metabolites
• Renal impairment
• Decompensated haemolytic anaemia
• Concurrent application of vital vaccines
• Cystitis
• Renal tract obstruction
• Active and uncontrolled infection
• Notice: myelosuppression and impaired hematopoietic function is not an exclusion criterion as this usual contraindication to the application to any of the IMPs will be overcome by the stem cell transplantation following conditioning therapy.

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