MAP to Provide Access to Nilotinib, for Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Managed Access Program (MAP) to Provide Access to Nilotinib, for Patients With Relapsed or Refractory Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)

The purpose of this Cohort Treatment Plan is to allow access to nilotinib for eligible patients diagnosed with relapsed or refractory Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL).

Currently, preliminary responses of nilotinib monotherapy in adults with refractory or relapsed Ph+ ALL show limited clinical benefit in this population of patients with a high unmet medical need. Remissions induced by imatinib are of short duration and resistance to imatinib represents a major clinical challenge. The exact benefit and role of nilotinib in this leukemia remains to be determined and requires further analysis. Until further data is available patients with Ph+ ALL should be treated with nilotinib through the Individual Patient Program.. Studies to date indicate that nilotinib may provide clinical benefit to Ph+ ALL patients and may represent a novel treatment option for these patients.

Inclusion Criteria:

The following criteria must be fulfilled for the provision of Managed Access and will vary depending on the stage of the product lifecycle:

• An independent request should be received from the Treating Physician (in some instances from Health Authorities, Institutions or Governments);
• The patient to be treated has a serious or life threatening disease or condition, and no comparable or satisfactory alternative therapy is available to monitor or treat the disease or condition;
• The patient is not eligible or able to enroll in a clinical trial;
• There is a potential patient benefit to justify the potential risk of the treatment use, and the potential risk is not unreasonable in the context of the disease or condition to be treated;
• Provision of the investigational product will not interfere with the initiation, conduct or completion of a Novartis clinical trial or overall development program and
• Such access provision as described above is allowed as per local laws and regulations.

Exclusion Criteria:

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

1. Male or Female patients age ≥ 18 years

2. WHO Performance Status of 0, 1 or 2

3. Relapsed or refractory Ph+ ALL

4. Imatinib (or dasatinib) must be discontinued at least 5 days prior to beginning therapy

5. Normal organ, electrolyte and marrow functions as described below:

   • Absolute Neutrophil Count (ANC) ≥ 1.0 x 1000000000/L
   • Platelets 50 x 1000000000/L
   • Potassium ≥ LLN (Lower limit of normal) or corrected to within normal limits with supplements prior to the first dose of nilotinib
   • Total calcium (corrected for serum albumin) ≥ LLN
   • Magnesium ≥ LLN or corrected to within normal limits with supplements prior to the first dose of nilotinib medication
   • AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x UL:N if considered due to tumor
   • Alkaline phosphatase ≤ 2.5 x ULN
   • Serum bilirubin ≤ 1.5 x ULN
   • Serum amylase and lipase ≤ 1.5 x ULN