A Phase III Randomized Trial of the Reduction of Chemotherapy in Philadelphia Chromosome-positive ALL of Young Adults

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02611492
• Date of registration: 19/11/2015
• Prospective Registration: Yes
• Primary sponsor: Assistance Publique - Hôpitaux de Paris
• Public title: A Phase III Randomized Trial of the Reduction of Chemotherapy in Philadelphia Chromosome-positive ALL of Young Adults GRAAPH2014
• Scientific title: A Phase III Study, Randomized, to Evaluate the Reduction of Chemotherapy Intensity in Association With Nilotinib (Tasigna®) in Philadelphia Chromosome-positive (Ph+) ALL of Young Adults (18-59 Years Old) (GRAAPH-2014)
• Date of first enrolment: April 2016
• Target sample size: 265
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02611492
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

France

Contacts

• Name: Hervé Dombret, MDPhD

• Name: Hervé Dombret, MDPhD

Key inclusion & exclusion criteria

Inclusion Criteria:

Patient

1. Whose blood and bone marrow explorations have been completed before the steroids
prephase

2. Aged 18-59 years old with newly-diagnosed non previously treated Ph+ ALL according to
WHO 2008 criteria (confirmed diagnosis of the Philadelphia chromosome defined by the
reciprocal translocation of chromosomes 9 and 22, t(9;22) and/or presence of the
BCR-ABL molecular maker)

3. With = 20% bone marrow blasts

4. With Eastern Cooperative Oncology Group (ECOG) Performans Status = 3

5. With or without central nervous system (CNS) or testis involvement

6. Without evolving cancer (except basal cell carcinoma of the skin or "in situ"
carcinoma of the cervix) or its chemo- or radio-therapy should be finished at least
since 6 months.

7. Having received no previous treatment for this hematological disease (including IT
injection)

8. Having signed written informed consent

9. With efficient contraception for women of childbearing age (excluding estrogens and
IUD)

10. With health insurance coverage

11. Who have received (or being receiving) the recommended steroid prephase.

Note 1: Secondary ALL (antecedent of chemo- or radio-therapy) can be included Note 2: In
case of high vascular risk (see section "study management") the patient will not be able to
receive nilotinib unless an ultra sound Doppler of the neck and lower limbs has been
performed during the pre-phase and treatment validated by the medical coordinators of the
protocol via the secretariat.

Exclusion Criteria:

Patient:

1. Previously treated with Tyrosine Kinase Inhibitor (TKI)

2. With another active malignancy

3. With general or visceral contra-indication to intensive therapy (except if considered
related to the ALL):

1. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x
upper limit of normal range (ULN)

2. Total bilirubin > 1.5 x ULN

3. Creatinine > 1.5 x ULN or creatinine clearance <50 mL/mn

4. Serum amylase or lipase > 1.5 x ULN or antecedents of acute pancreatitis

4. With heart failure, including at least one of the following criteria:

1. Left ventricular ejection fraction (LVEF) <50% or below the lowest normal
threshold, as determined by ECG or heart failure (NYHA grade III or IV)

2. Impossibility to measure the QT interval on ECG

3. Complete left bundle branch block

4. Pacemaker

5. Congenital long QT syndrome of known familial antecedents of long QT syndrome

6. Antecedents or current ventricular or atrial tachyarrhythmia, clinically
significant

7. Baseline bradycardia (<50 bpm) clinically significant

8. Corrected QT interval (QTc)> 450 msec established on the mean of 3 baseline ECG

9. Antecedents of myocardial infarct in the past 6 months

10. Instable angor within the past 12 months

11. Any heart condition clinically significant (i.e. congestive heart failure,
uncontrolled hypertension)

5. Active uncontrolled infection, any other concurrent disease deemed to interfere with
the conduct of the study as judged by the investigator

6. Severe evolving infection, or known HIV or Human T-Lymphotropic Virus type I (HTLV1)
seropositivity, or active infection by hepatitis B or C virus

7. Pregnant (beta-HCG) or nursing woman

8. Women of childbearing potential not willing to use an effective form of contraception
during participation in the study and at least three months thereafter. Patient not
willing to ensure not to beget a child during participation in the study and at least
three months thereafter.

9. Having received an investigational treatment or participation in another trial within
30 days prior to entering this study.

10. Not able to bear with the procedures or the frequency of visits planned in the trial.

11. Unable to consent, under tutelage or curators, or judiciary safeguard



Age minimum: 18 Years
Age maximum: 59 Years
Gender: All

Health Condition(s) or Problem(s) studied

Philadelphia Chromosome Positive Adult Acute Lymphoblastic Leukemia

Intervention(s)

Drug: Depomedrol

Drug: 6 Mercaptopurine (6MP)

Drug: Dexamethasone

Drug: Imatinib

Drug: Vincristine

Drug: Nilotinib

Drug: Aracytine (Ara C)

Drug: Granulocyte Colony-Stimulating Factor (G-CSF)

Drug: Methotrexate

Primary Outcome(s)

Major Molecular Response (MMolR) [Time Frame: 4 cycles (4 months)]

Secondary Outcome(s)

Cumulative incidence of relapse [Time Frame: 10 years]

Cumulative incidence of treatment- and transplantation-related mortality [Time Frame: 2 years]

Event-free survival [Time Frame: 10 years]

T315I mutation [Time Frame: 10 years]

Toxicity [Time Frame: 12 months]

overall survival [Time Frame: 10 years]

Complete remission after cycle 1 [Time Frame: day 28]

Relapse free survival [Time Frame: 10 years]

Secondary ID(s)

AOM12629_1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors