TRICE MiniAlloGleevec
Trial overview
Phase I/II study of the adjunctive use of Nilotinib in patients undergoing reduced intensity allogeneic transplantation for Imatinib resistant or intolerant Chronic Myeloid Leukaemia.
Tasigna in reduced intensity conditioning transplantation evaluation study.
Inclusion criteria
1. BCRABL positive CML in first chronic phase:
• <15% blasts in peripheral blood and bone marrow
• <30% blasts plus promyelocytes in peripheral blood and bone marrow
• <20% basophils in the peripheral blood
• ≥50 x 109/L (≥50,000/mm3) platelets
• No evidence of extramedullary leukaemic involvement, with the exception of liver and spleen
2. Resistant or intolerant to imatinib mesylate:
Imatinib resistance in CML-CP includes patients who meet objective criteria for persistent disease or disease progression during imatinib therapy as outlined in Both i and ii:
i) Any of the following occurring during imatinib therapy:
• Patients who have failed to achieve CHR after 3 months of imatinib therapy or have lost a CHR
• Loss of CHR defined as any of the following documented 2 times, at least 2 weeks apart:
1. WBC ≥ 20 x 109/L and not attributable to other causes (e.g infection)
2. Platelet count ≥ 600 x 109/L
3. Appearance of >5% myelocytes+metamyelocytes in the peripheral blood
4. Appearance of blasts or promyelocytes in the peripheral blood
5. Splenomegaly to a size > 5cm below the left costal margin
• Patients who have failed to achieve at least a minimal cytogenetic response after 6 months of imatinib therapy or patients who have lost minimal cytogenetic response documented on 2 separate occasions
• Patients who have failed to achieve a major cytogenetic response after 12 months of imatinib therapy or patients who have lost a major cytogenetic response documented on 2 separate occasions
• Cytogenetic relapse, defined by ≥30% increase in bone marrow Ph+ metaphase cells, documented on 2 separate occasions
• Clonal evolution
ii) Patients otherwise eligible for study receiving <600mg imatinib per day (400mg per day at clinical discretion) must be treated with ≥600mg per day for a minimum of 3 months, unless they meet the criteria outlined below for the definition of imatinib intolerance, or unless there is a disease progression defined as any of the following:
• Doubling of any of the following: total peripheral WBC, basophils, blasts or platelets, documented on 2 separate occasions atleast one week apart
• Development of grade 3 or 4 disease-related symptoms (bone pain, fever, weight loss, anorexia)
• The presence of one of the following amino acid mutations detected by direct sequencing: L248, G250, Q252, Y253, E255, T315, F317, H396
Imatinib intolerance (at any dose and/or duration) includes patients who have discontinued imatinib therapy due to Grade 3 or 4 adverse events that persist in spite of optimal supportive care measures, for example: skin rash, fluid retention, cardiopulmonary events, thrombocytopenia, liver function abnormalities, and diarrhoea. In addition, Grade 2 adverse events related to imatinib therapy, in spite of optimal supportive care measures and that persist for one month or that recurs for more than 3 times whether the dose is reduced or discontinued will also qualify patients as intolerant.
3. Age ≥ 18 years
4. Patients with an HLA identical sibling donor or a suitable matched unrelated donor
5. Patients considered fit for transplantation
6. Patients must be able to swallow capsules
7. Liver Function < 2.5 upper limit of normal
8. In patients with magnesium and potassium levels below the LLN, every attempt should be made to normalise levels.
9. All men & women of child bearing potential must agree to practice effective contraception during the entire study period.
10. CML patients who have been treated with an investigational tyrosine kinase inhibitor who otherwise meet the definition or imatinib-resistance or intolerance are eligible.
11. Give written informed consent prior to study specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.
12. Be willing and able to comply with the protocol for the duration of the study
Exclusion criteria
1. Patients with an allergy to Fludarabine, Busulphan, Campath or Nilotinib
2. “BCRABL negative” CML
3. Pregnant or lactating women.
4. Patients with organ allografts
5. Impaired cardiac function, including any one of the following:
• LVEF <40% or below the institutional lower limit of the normal range (whichever is higher) as determined by MUGA scan or echocardiogram
• Complete left bundle branch block
• Use of a ventricular-paced pacemaker
• Congenital long QT syndrome
• History of or presence of clinically significant ventricular or atrial tachyarrhythmias
• Clinically significant resting bradycardia (<50 beats per minute)
• QTc > 450 msec on screening ECG (using the QTcF formula). If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTc criterion
• Right bundle branch block plus left anterior hemiblock, bifascicular block
• Myocardial infarction within 12 months prior to starting nilotinib
• Other clinically significant heart disease (eg unstable angina, congestive heart failure, uncontrolled hypertension).
6. Patients with any other condition, which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial.
Contact details
Other trials currently active for Transplant
A phase III randomised study to investigate the use of adoptive cellular therapy (ACT) in combination with conventional antiviral drug therapy for the treatment of CMV reactivation episodes in patients following allogeneic haematopoietic stem cell transplant
TRANSPLANTATION OF UMBILICAL CORD BLOOD FROM UNRELATED DONORS IN PATIENTS WITH HAEMATOLOGICAL DISEASES USING A REDUCED INTENSITY CONDITIONING REGIMEN
Tags
phase i/ii reduced intensity allogeneic transplantation imatinib chronic myeloid leukaemia. tasigna reduced intensity conditioning transplantation trice