Main info

Identifier:

HO142 CML

Sponsor:

GIMEMA

Working group party:

CML/MPN

Age:

>= 18

Stage:

2nd Line

Echelon:

Level C-HIC

Included patients:

26

(of 26)

Active sites:

9

(of 17)

Title:

Sustained treatment-free remission in BCR-ABL+ chronic myeloid leukemia: a prospective study comparing Nilotinib versus Imatinib with switch to Nilotinib in absence of optimal response.

Timeline

News

Flow

Details

Phase:

Prospective randomized Phase III study

Monitoring Type:

Study Specific

Objectives:

Primary Objective
The study will investigate in newly diagnosed CP-CML patients the efficacy of NIL frontline therapy vs IM followed by switch to NIL in the case of absence of optimal response as defined by the ELN criteria using two primary end-points:
− To evaluate the rates of molecular response (MR4.5) at 24 months
− To evaluate the rate of patients who remain in sustained treatment free remission (≥MR3.0) without molecular relapse 12 months after entering the TFR phase. The molecular relapse is defined as loss of MMR, or confirmed loss of MR3.0.

Secondary Objectives
1. Monitoring the molecular response.
2. Progression-free survival (PFS) in the two arms of the study.
3. Overall Survival in the two arms of the study.
4. Rates of major molecular response (MR3.0) during the study in the two arms of the study.
5. The dynamics of molecular response
6. The relationship between baseline characteristics and the primary objectives
7. The relationship between early molecular response and the primary objectives
8. To assess the safety profile of both arms.
9. To determine the rate and the time-distribution of the discontinuation causes of the first-line TKI.
10. To investigate quality of life (QoL) differences between treatment arms over time

Eligibility

Inclusion Criteria:

Patients eligible for inclusion in this study have to meet all of the following criteria:

• Patients with a confirmed diagnosis of BCR/ABL+ CML in chronic phase
• Documented chronic phase CML must meet all the following criteria:
  • < 15% blasts in peripheral blood
  • < 30% blasts plus promyelocytes in peripheral blood
  • < 20% basophils in the peripheral blood
  • ≥ 100 x 109/L (≥ 100,000/mm3) platelets
• Age ≥18
• ECOG performance status of 0-2
• Evidence of typical BCR-ABL transcripts which are amenable to standardized RQ-PCR
• Adequate end organ function as defined by:
  • Total bilirubin < 1.5 x ULN (ULN = upper limit of normal in a local institution lab). Does not apply to patients with isolated hyperbilirubinemia (e.g., Gilbert’s disease) grade < 3
  • SGOT (AST) and SGPT (ALT) ≤ 3 x ULN
  • Serum amylase and lipase ≤ 2 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Serum creatinine < 1.5 x ULN
• Written informed consent prior to any study procedures.

Exclusion Criteria:

• Previous treatment with BCR-ABL inhibitors for more than 30 days.
• Expression of any atypical BCR-ABL transcripts, instead of the classical P210-encoding type with the e13a2 or the e14a2 junction at screening.
• Previous anticancer agents (hydroxyurea, anagrelide, interferon) for CML for more than three months.
• Poorly controlled diabetes mellitus (defined as HbA1c >8%)
• Prior documented history of coronary heart disease, including myocardial infarction, coronary bypass, coronary stent, and symptomatic angina as defined at page 30 in Exclusion Criteria.
• Uncontrolled hypertension
• History of peripheral arterial occlusive disease.
• History of acute pancreatitis within 12 months of study entry, or a past medical history of chronic pancreatitis.
• Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers which cannot be either discontinued or switched to a different medication prior to starting study drug.
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and for which cannot be either safely discontinued or switched to a different medication prior to starting study drug.
• Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
• Patients unable to understand and to comply with study instructions and requirements.
• Refusal to give informed consent.

Registration Details

Participating Sites

= Active hospitals

= Inactive hospitals