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

Study Overview
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Brief Summary
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A prospective Phase II clinical study to assess the efficacy and toxicity of high dose chemotherapy (HDT) followed by allogeneic stem cell transplantation (allo- or autoSCT) as treatment of primary progressive and relapsed aggressive Non-Hodgkin Lymphoma (NHL) - ASTRAL

Detailed Description
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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.

Official Title
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A Prospective Phase II Clinical Study to Assess the Efficacy and Toxicity of High-dose Chemotherapy Followed by Allogeneic Stem Cell Transplantation as Treatment of Primary Progressive and Relapsed Aggressive Non-Hodgkin Lymphoma

Conditions
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Aggressive Non-hodgkin Lymphoma (aNHL), Lymphoma, B-Cell, Lymphoma, T-Cell

Intervention / Treatment
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* Drug: High dose chemotherapy before allogeneic stem cell transplantation (alloSCT)
* Procedure: Bone marrow histology
* Diagnostic Test: clinical and laboratory parameters
* Diagnostic Test: PET-CT or CT


Participation Criteria
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Eligibility Criteria
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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. -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: alloSCT<br>defined high-dose chemotherapy (HDT) followed by allogeneic stem cell transplantation (alloSCT) | Drug: High dose chemotherapy before allogeneic stem cell transplantation (alloSCT)<br>* High-dose therapy (HDT) prior to alloSCT will consist of FTC<br>* Other names: fludarabine, thiotepa ,cyclophosphamide (FTC);Procedure: Bone marrow histology<br>* Bone marrow histology at staging and restaging is only mandatory if the bone marrow was initially involved<br>Diagnostic Test: clinical and laboratory parameters<br>* During staging and restaging examinations, all clinical and laboratory parameters relevant for therapy.<br>Diagnostic Test: PET-CT or CT<br>* Metabolic CR in a PET-CT scan after the last cycle of therapy prior to planned SCT. Consists preferably of a PET-CT or a CT scan according to local practice and other appropriate diagnostic procedures with respect to the sites of primary involvement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of efficacy variables, Rate of Progression free survival (PFS) | To compare a defined high dose therapy (HDT) with study medication followed by alloSCT lead to treatment results in terms of PFS, that are better than results obtained with high-dose therapy and autoSCT in a comparable Patient Population ( historical data). | 1 year after SCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of efficacy variables, Rate of complete remissions (CR) | Number of complete remissions divided by the number of patients (CR), | 1 year after stem cell transplantation (SCT) | 
| Measurement of efficacy variables, Rate of partial remissions (PR) | Number of partial remissions divided by the number of patients (PR); | 1 year after SCT | 
| Measurement of efficacy variables, Rate of complete and partial remissions (ORR) | Number of complete and partial remissions divided by the number of patients (ORR); | 1 year after SCT | 
| Measurement of efficacy variables, Rate of progressive diseases (PD) | Number of progressive diseases after SCT divided by the number of patients (PD); | 1 year after SCT | 
| Measurement of efficacy variables, Rate of relapse (RR) | safety item | 1 year after SCT | 
| Measurement of efficacy variables, Rate of treatment-related mortality | treatment-related death divided by the number of patients | 1 year after SCT | 
| Rate of event free survival at 1 year (EFS) | safety item | 1 year after SCT | 
| Measurement of efficacy variables, Rate of overall survival at 1 year (OS) | safety item | 1 year after SCT | 
| Measurement of efficacy variables, Rate of non-relapse mortality (NRM) | safety item | 1year after SCT | 
| Measurement of efficacy variables, Causes of death | safety item | 1year after SCT | 
| Measurement of efficacy variables, Incidence and severity of acute and chronic graft versus host disease (GvHD); | safety item | until the last Follow-Up Visit ( 1-2 Year after SCT) | 
| Measurement of efficacy variables, Adverse events (AEs) grade 3 and 4 | safety item | until about day 100 after SCT. | 
| Measurement of efficacy variables, Serious adverse events (SAEs) | safety item | until about day 100 after SCT. | 
| Measurement of number of blood cells | recovery of White blood cells and platelets | 1year after SCT | 
| Measurement of efficacy variables, Rate of infections | safety item | 1year after SCT |