Clinical trial NCT04121507: ASTRAL- a Clinical Study to Assess the Efficacy and Toxicity of High-dose Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aggressive Non-hodgkin Lymphoma (aNHL)
Lymphoma, B-Cell
Lymphoma, T-Cell
Lead sponsor: GWT-TUD GmbH
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

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

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

   1. B-Cell non-hodgkin lymphoma (B-NHL) or
   2. T-Cell non-hodgkin lymphoma (T-NHL):
6. Staging at relapse or progression (data should not be older than 4 weeks):
7. Staging after 2 or 3 cycles of salvage treatment:
8. Donor availability:
9. 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
10. 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
11. Females of non-childbearing potential:

Exclusion Criteria:

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

1. Pregnant females; lactating women must end breast feeding before start of study treatment
2. Serious accompanying disorder or impaired organ function
3. Central nervous system (CNS) involvement of lymphoma - to be examined in case of clinical symptoms
4. History of severe cardiac diseases, and cardiac function impairment
5. Severe kidney disease
6. HIV-positivity
7. Hepatitis B and C as defined by seropositivity
8. Patients under legal guardianship regarding medical decisions
9. Ongoing treatment or study procedures within any other clinical trial with the exception of follow up
10. Ongoing exclusion periods of other clinical studies after end of treatment
11. 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
12. Subjects with known hypersensitivity to the study drugs
13. 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
14. Commitment to an institution by virtue of an order issued either by the judicial or the administrative authorities
15. Dependency on the sponsor, trial site or investigator
16. Additional exclusion criteria with respect to summary of product characteristics (SmPC) of the investigational medical product (IMPs) fludarabine, thiotepa, cyclophosphamide:

    1. Known hypersensitivity to fludarabine, thiotepa, cyclophosphamide or one of their metabolites
    2. Renal impairment
    3. Decompensated haemolytic anaemia
    4. Concurrent application of vital vaccines
    5. Cystitis
    6. Renal tract obstruction
    7. Active and uncontrolled infection
    8. 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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Primary outcomes:
measure: Measurement of efficacy variables, Rate of Progression free survival (PFS)
timeFrame: 1 year after SCT
Secondary outcomes:
measure: Measurement of efficacy variables, Rate of complete remissions (CR)
timeFrame: 1 year after stem cell transplantation (SCT)
measure: Measurement of efficacy variables, Rate of partial remissions (PR)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of complete and partial remissions (ORR)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of progressive diseases (PD)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of relapse (RR)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of treatment-related mortality
timeFrame: 1 year after SCT
measure: Rate of event free survival at 1 year (EFS)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of overall survival at 1 year (OS)
timeFrame: 1 year after SCT
measure: Measurement of efficacy variables, Rate of non-relapse mortality (NRM)
timeFrame: 1year after SCT
measure: Measurement of efficacy variables, Causes of death
timeFrame: 1year after SCT
measure: Measurement of efficacy variables, Incidence and severity of acute and chronic graft versus host disease (GvHD);
timeFrame: until the last Follow-Up Visit ( 1-2 Year after SCT)
measure: Measurement of efficacy variables, Adverse events (AEs) grade 3 and 4
timeFrame: until about day 100 after SCT.
measure: Measurement of efficacy variables, Serious adverse events (SAEs)
timeFrame: until about day 100 after SCT.
measure: Measurement of number of blood cells
timeFrame: 1year after SCT
measure: Measurement of efficacy variables, Rate of infections
timeFrame: 1year after SCT
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: HELIOS Klinik Berlin-Buch, Klinik für Hämatologie und Stammzelltransplantation
state: Brandenburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Medizinische Klinik II
city: Bochum
country: Germany
facility: Medizinisches Universitätsklinikum
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Dresden, Medzinische Klinik I
city: Düsseldorf
country: Germany
facility: Universitäsklinikum Düsseldorf
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen Klinik für Hämatologie/Med. Onkologie
city: Halle
country: Germany
facility: Universitätsklinikum Halle
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie, Interdisziplinäre Klinik und Poliklinik für Stammzelltransplantation
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Medizinische Klinik, Innere Medizin V
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Innere Medizin, Abtl. Hämatologie und Innternistische Onkologie
city: Münster
country: Germany
facility: Universitätsklinikum Münster, KMT-Zentrum/ Med. Klinik A
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
Study officials:
affiliation: Helios Klinikum Berlin-Buch
name: Bertram Glass, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: