Content - GRAALL 2014

Optimizing the chemotherapy for the treatment of leukemia

The trial GRAALL-2014 builds on GRAALL-2003 and 2005 and investigates the acute lymphoblastic leukemia (ALL) of the T- and B-line. This kind of chancer is a disease of the white blood cells that causes them to spawn uncontrollably. Sickened white blood cells carry an increased amount of leukemia cells (that cause the spawning) and are found in the bone marrow and sometimes in the blood. Normal blood components are suppressed through this process.   

GRAALL-2014 is divided into three sub-trials: ALL of the B- and T-line and of the Philadelphia-positive form (Ph+). Each group identifies the existence of a certain gene at the time of the diagnosis.  

Adjusting the therapy to the age

On the one hand, the treatment with a drug for chemotherapy (Methotrexat) will be increased for patients within the age of 18 and 44 years. The goal hereby is to increase the spread of the drug in the central nervous system, what decreases the needed intensity of the following radiotherapy.  On the other hand, patients within the age of 45 and 59 years receive a less intensive chemotherapy, in order to reduce the side effects. The trial suggests to limit the time patients receive corticoids (cortisone) and to decrease the doses of L-asparaginase (enzyme) and anthracyclines (antibiotics). These active substances hinder cells from growing.   

Through this adaption, patients receive chemotherapy adjusted to their age. Depending on how patients respond to the therapy, the study suggests a transplantation of stem cells in the bone marrow (hematopoietic stem cells).  

Trial goal

GRAALL-2014/B and GRAALL-2014/T have the goal to improve tolerance and outcome of the chemotherapy. This goal shall be achieved through adjustment of the therapy for ALL of the B- and T-line to the age of the patients and characterization of the disease.  

GRAAPH-2014 has the goal to improve the outcome of the chemotherapy in combination with tyrosine kinase inhibitors (TKI) for Ph+ALL. Tyrosine kinase inhibitors block the enzyme of the tyrosine kinase that would make leukemia cells multiply themselves uncontrollably. The drug TKI Nilotinib (Tasigna®) might enable to reduce the dose of the standard chemotherapy.  

Trial duration and scope

The treatment for patients, who are participating in this study, lasts five years. Whereat, the therapy and follow-up observation each lasts two and a half years. The trial itself lasts then years and is conducted in several hematological centers in France, Belgium and in Switzerland.

500 patients in the age between 18-59 years, who are suffering from a B-ALL, are able to participate in the sub-trial GRAALL-2014/B. GRAALL-2014/T allows 275 patients in the age between 18-59 years, who are suffering from T-ALL, to participate. In the sub-trial GRAAPH-2014 can 265 patients participate, who are suffering from Ph+ ALL and are in the age between 18-59 years.

Study Chair:

Prof. Dr. med. Yves Chalandon, University Hospital of Geneva, +41 22 372 98 70

  • Contacts at the hospitals

  • Inclusion criteria

    • Whose blood and bone marrow explorations have been completed before the steroids prephase
    • aged from 18 to59 years old with a not previously treated (including IT injection) T-ALL newly-diagnosed according to the WHO 2008 definition with > 20% bone marrow blasts
    • With ECOG < 3
    • With or without central nervous system (CNS) involvement or testis
    • Without other evolving cancer (except basal cell carcinoma of the skin and ―in situ‖ carcinoma of the cervix) or its treatment should be finished at least since 6 months
    • Having signed a written informed consent
    • With efficient contraception for women of childbearing age (excluding estrogens and IUD)
    • Having received or being receiving the recommended steroid prephase
    • With health insurance coverageSecondary ALL (antecedent of chemo- or radio-therapy) can be included
  • Exclusion criteria

    • With lymphoblastic lymphoma and bone marrow blasts < 20%, Burkitt-type ALL or with antecedents of chronic myeloid leukemia (CML) or other myeloproliferative neoplasm
    • With contra-indication to anthracyclines or any other general or visceral contra-indication to intensive therapy except if considered related to the ALL:
      • Aspartate transaminase (AST) and/or alanine transaminase (ALT) > 5 x upper limit of normal range (ULN)
      • Total bilirubin ≥ 2.5 x upper limit of normal range (ULN)
      • Creatinine > 1.5 x upper limit of normal range (ULN) or creatinine clearance <50 mL/mn
    • Myocardial infarction within 6 months prior to inclusion in the trial, cardiomyopathy (NYHA grade III or IV), left ejection ventricle fraction (LEVF) < 50% and/or RF < 30%,
    • Active severe infection or known seropositivity for HIV or Human T cell leukemia/lymphoma virus type 1 (HTLV-1) or active hepatitis B or C
    • Other active malignancy
    • Pregnant (beta-Human Chorionic Gonadotropin (hCG) positive) or nursing woman
    • Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
    • Treated with any other investigational agent or participation in another trial within 30 days prior to entering this study
    • Not able to bear with the procedures or the frequency of visits planned in the trial
    • Unable to consent, under tutelage or curators, or judiciary safeguard

Locations for this trial:

Kantonsspital Aarau
Tellstrasse 25
0 5001 Aarau
Istituto Oncologico della Svizzera Italiana IOSI
Via Ospedale
0 6500 Bellinzona
Inselspital
Freiburgstrasse 8
3010 Bern
Universitätsspital Basel
Petersgraben 4
0 4031 Basel
Hôpital Fribourgeois HFR
Chemin des Pensionnats 2
1708 1708 Fribourg
Hôpitaux Universitaires de Genève HUG
Rue Gabrielle-Perret-Gentil 4
0 1205 Genève
Centre Hospitalier Universitaire Vaudois CHUV
Rue du Bugnon 46
0 Lausanne
Kantonsspital Luzern
Spitalstrasse
0 6000 Luzern
Kantonsspital St. Gallen
Rorschacher Strasse 95
0 9007 St. Gallen
UniversitätsSpital Zürich
Rämistrasse 100
0 8091 Zürich