A Notch Signalling Pathway Inhibitor for Patients With T-cell Acute Lymphoblastic Leukemia/Lymphoma (ALL)(0752-013)

A Phase I Study of a Gamma Secretase Inhibitor for Adult and Pediatric Patients With Relapsed or Refractory Acute T-Cell Lymphoblastic Leukemia and Lymphoma

A Notch signalling pathway inhibitor study in pediatric and adult patients with relapsed (worsening) or refractory (not responding to treatment) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL).

Inclusion Criteria:

• Patients must have pathologically documented precursor T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), relapsed or refractory to standard therapy, or not be a candidate for standard myelosuppressive chemotherapy due to age or comorbid disease.
• Patient must have performance status <2 on the ECOG performance status for patients >16 years old; Lansky performance level >50 for patients 12 months to less than or equal to 16 years old.
• Patient must have adequate renal and liver function as indicated by the laboratory values performed within 14 days of receiving the first dose of study drug.
• Patient must have fully recovered from any chemotherapy and be greater than 2 weeks from radiotherapy, immunotherapy, or systemic steroid therapy with the exception of hydroxyurea, intrathecal therapy, or immunosuppressant therapy for chronic graft-versus-host disease prophylaxis following allogeneic bone marrow transplant.
• Patient must be greater than 2 months following bone marrow or peripheral blood stem cell transplantation and off all immunosuppressant therapy (with the exception of patients taking immunosuppressant therapy for chronic graft-versus-host disease prophylaxis following allogeneic bone marrow transplant).
• Men and women of reproductive potential must use an effective contraceptive method while enrolled in the study.
• Patient or the patient's legal representative must be able to understand the study and give written informed consent.

Exclusion Criteria:

• Patient has had treatment with any investigational therapy during the preceding 30 days.
• Patient has uncontrolled congestive heart failure, angina, or had a myocardial infarction in the preceding 3 months.
• Patient has known hypersensitivity to the components of study drug, its analogs, or to allopurinol.
• Patient has active or uncontrolled infection.
• Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patient is pregnant or lactating.
• Patient has any other severe concurrent disease which would make the patient inappropriate for entry into this study.
• Patient is known to be HIV positive or who has an AIDS-related illness.
• Patients with a "currently active" second malignancy, other than non-melanoma skin cancer should not be enrolled.
• Patient has isolated CNS disease.