Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00003910

Trial Description

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Title

International Study for Treatment of Standard Risk Childhood Relapsed ALL 2010 A Randomized Phase III Study Conducted by the Resistant Disease Committee of the International BFM Study Group

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

The main goal of this study is to improve the outcome of children and adolescents with
standard risk first relapsed acute lymphoblastic leukemia. Furthermore, goal is to set up a
large international study group platform allowing for optimization of standard treatment
strategies and integration of new agents.

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Brief Summary in Scientific Language

ALL is the most frequent malignancy in childhood and has favourable event-free and overall
survival rates. About 15% of patients suffer relapse. At relapse prognosis is much inferior
(about 50% survival) leukemic clones exhibit much more resistance to conventional
chemotherapy. Patients with relapse require treatment intensification and different
therapeutic strategies. At relapse, new targeted agents can provide the chance for better
cure rates and need to be investigated in prospective controlled trials before they may be
even eligible for frontline treatment strategies.

The IntReALL SR 2010 trial is designed to achieve 2 major aims: Establishment of the best
available standard chemotherapy treatment. This is addressed with the randomization of the 2
best developed strategies for treatment of childhood relapsed ALL, the German ALL-REZ BFM
2002 Protocol with the Protocol II IDA arm, and the British ALL-R3 protocol with the
mitoxantrone arm. This randomization allows confirming the feasibility of both protocols in
a large variety of different countries and study groups with different frontline therapy
strategies. As result from this trial a common standard chemotherapy for childhood relapsed
ALL will be developed which can serve as backbone for investigation of the most attractive
targeted new agents.

The 2nd aim is the investigation of the efficacy and tolerability of the humanized CD22
directed monoclonal antibody Epratuzumab, manufactured and provided by the company
Immunomedics, US. The drug will be randomly added to the respective consolidation
chemotherapy, using EFS as primary endpoint. Epratuzumab has been developed in adult
rheumatology indications and in B-cell malignancies. A phase I and early phase II
combination trial in childhood relapse ALL has been conducted and published by the
Children's Oncology Group (COG), and results of an extended phase II trial have been
recently presented at the ASH meeting (12/2011). The drug showed a very favourable safety
profile as single drug and in combination with multidrug chemotherapy. Activity was
moderate, the recent trial showed a significantly better elimination of minimal residual
disease (MRD) in patients achieving a 2nd complete remission. This finding supports the
strategy to use Epratuzumab in combination with consolidation chemotherapy after induction
in patients having reduced the leukemia burden in the bone marrow to at least below 25%,
most of them will be in 2nd complete remission. Epratuzumab will be given weekly at the
established dose. Pharmacokinetics will be investigated in a reduced number of patients. The
further treatment will be conventional intensive chemotherapy and maintenance therapy in
patients with good MRD response after induction, or with allogeneic stem-cell
transplantation (SCT) in those with insufficient MRD response. SCT will be considered as
standard treatment element and will not lead to censoring of the patients of considered as
endpoint. Epratuzumab is not licensed so far and the trial may add to the approval process
in case.

Scientific advice for the trial has been requested at the FDA and the EMA. Both institutions
have responded supportively. Concerns and recommendations of FDA and EMA have been addressed
in the protocol and the corresponding statistical analysis plan.

The IntReALL SR 2010 trial will be financed within the FP7 project IntReALL 2010 supported
by the European Commission. Within the project next to the SR trial a strategy for HR
patients will be addressed, the establishment of harmonized diagnostic procedures, an
international tumour bank and a comprehensive biologic/scientific programme will be set up,
a web-based GCP conform database will be established, a comprehensive statistical strategy
for both trials are established, and drug development in this indication will be promoted
and organized from side of the disease experts in cooperation with the established academic
structures ITCC (Innovative Therapies for Children with Cancer), the ENCCA project (European
Network for Cancer in Children and Adolescents) and SIOPe (International Society for
Pediatric Oncology Europe), the central authorities (EMA, FDA) and Industry. Parent
organisation and former patients are integrated into and accompany the process.

Main aims of the IntReALL FP7 project are to establish a therapeutic platform for children
with relapsed ALL in Europe and beyond and to give them access to the most promising new
agents under academic control and free from commercial interests.

Randomized evidence for efficacy and tolerability of new drugs are demanded by competent
authorities. These trials are conducted beyond the mostly palliative patient group eligible
for phase I/II trials in curative indications. Treatment protocols for with curative
indications need to be conducted in the best interests of the patients, ideally with an
academic sponsor. The design should be driven by medical and scientific evidence and not by
commercial interests as is the case in industry sponsored trials. This concept was
acknowledged by the European Commission selecting the project for funding from many other
powerful applications.

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Organizational Data

  •   DRKS00003910
  •   2014/04/25
  •   2013/02/18
  •   yes
  •   [---]*
  •   [---]*
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Secondary IDs

  •   NCT01802814  (ClinicalTrials.gov)
  •   IntReALL SR 2010  (University Hospital of Berlin)
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Health Condition or Problem studied

  •   Acute Lymphoblastic Leukemia (ALL)
  •   C91.0 -  Acute lymphoblastic leukaemia
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Interventions/Observational Groups

  •   Drug: SR-A + Epratuzumab
  •   Drug: SR-B + Epratuzumab
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group), Control group receives no treatment
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
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Primary Outcome

- SR induction/consolidation ALL-REZ BFM 2002 versus UK-ALL-R3 (randomisation 1); time frame: at 4 years of arm A; SR induction/consolidation ALL-REZ BFM 2002 versus UK-ALL-R3 (randomisation 1): 10% pEFS superiority of arm B above a 65% pEFS at 4 years of arm A
- SR consolidation +/- epratuzumab (randomisation 2); time frame: at 4 years of standard arm; SR consolidation +/- epratuzumab (randomisation 2): 10% pEFS superiority of the arm with epratuzumab above an expected 74% pEFS at 4 years of the standard arm

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Secondary Outcome

- SR induction/consolidation; time frame: year 7; SR induction/consolidation: comparison of OS, toxicity, rate of CR2, and rate of MRD between treatment groups
- SR consolidation +/- epratuzumab; time frame: year 7; SR consolidation +/- epratuzumab: comparison of OS, toxicity, MRD levels, rate of MRD and evaluation of pharmacokinetic parameters of Epratuzumab

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Countries of Recruitment

  •   Australia
  •   Austria
  •   Belgium
  •   Czech Republic
  •   Denmark
  •   Finland
  •   France
  •   Germany
  •   Ireland
  •   Israel
  •   Italy
  •   Japan
  •   Netherlands
  •   Norway
  •   Poland
  •   Portugal
  •   Sweden
  •   Switzerland
  •   United Kingdom
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Locations of Recruitment

  •  
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Recruitment

  •   [---]*
  •   2013/06/30
  •   1242
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   no minimum age
  •   17   Years
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Additional Inclusion Criteria

- Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL

- Children less than 18 years of age at inclusion

- Meeting SR criteria: late isolated or late/early combined BCP BM relapse, any
late/early isolated extramedullary relapse

- Patient enrolled in a participating centre

- Written informed consent

- Start of treatment falling into the study period

- No participation in other clinical trials 30 days prior to study enrolment that
interfere with this protocol, except trials for primary ALL Inclusion criteria
specific for the epratuzumab randomization

- Precursor B-cell immunophenotype. A specific CD22 expression level is not required

- M1 or M2 status of the bone marrow after induction

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Exclusion Criteria

- BCR-ABL / t(9;22) positive ALL

- Pregnancy or positive pregnancy test (urine sample positive for β-HCG > 10 U/l)

- Sexually active adolescents not willing to use highly effective contraceptive method
(pearl index <1) until 2 years after end of antileukemic therapy

- Breast feeding

- Relapse post allogeneic stem-cell transplantation

- The whole protocol or essential parts are declined either by patient himself/herself
or the respective legal guardian

- No consent is given for saving and propagation of pseudonymized medical data for
study reasons

- Severe concomitant disease that does not allow treatment according to the protocol at
the investigator's discretion (e.g. malformation syndromes, cardiac malformations,
metabolic disorders)

- Karnovsky / Lansky score < 50%

- Subjects unwilling or unable to comply with the study procedures

- Subjects who are legally detained in an official institute

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Addresses

  • start of 1:1-Block address primary-sponsor
    • University Hospital of Berlin
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    •   [---]*
    •   [---]*
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    • University Hospital of Berlin - Charité
    • Arend von Stackelberg, MD 
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    •   [---]*
    •   [---]*
    •   [---]*
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  • start of 1:1-Block address public-contact
    • Arend von Stackelberg, MD 
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Sources of Monetary or Material Support

  • [---]*
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Status

  •   Recruiting planned
  •   [---]*
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   361
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.