Dose Escalation Study of CAL-101 in Select Relapsed or Refractory Hematologic Malignancies

A Phase 1, sequential dose escalation followed by cohort expansion study of CAL-101, an oral inhibitor of PI3K delta, in patients with relapsed or refractory CLL, select B-cell NHL and AML.

Inclusion criteria

• Age > or = 18.
• Has relapsed or refractory disease as defined by the following:

• CLL - refractory to or relapsed after at least 2 prior therapies, including fludarabine, alone or in combination. Patients should not be eligible for transplantation (patients who are candidates for transplantation and have declined transplantation are eligible for this study).
• B-cell NHL - refractory to or relapsed after at least 1 prior chemotherapy regimen and having received rituximab as a single agent or in combination with other therapies.
• AML - refractory to or relapsed after at least 1 cycle of induction chemotherapy. Patients over the age of 70 who are not appropriate candidates for chemotherapy are eligible for this study.
• MM - refractory to or relapsed after at least 2 prior chemotherapy regimens, including bortezomib and thalidomide or lenalidomide (except if the drug is contraindicated in a patient then this requirement is waived).
• Disease status requirement:

• For CLL patients, symptomatic disease that mandate treatment.
• For B-cell NHL patients, has measurable disease by CT scan.
• For AML patients, has > 10% blasts in the bone marrow for refractory or relapsed disease and > 20% blasts in the bone marrow if no prior chemotherapy.
• For MM patients, has measurable disease defined by at least 1 of the following 3 measurements: serum M-protein > or = to 1 g/dL, urine M-protein > or = to 200 mg/24 h, or serum free light chain (FLC) assay with involved FLC level > or = to 10 mg/dL provided serum FLC ratio is abnormal.
• WHO performance status of ≤ 2.
• For men and women of child-bearing potential, willing to use adequate contraception (i.e., latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.
• Is able to provide written informed consent.

Exclusion criteria

• Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to screening.
• For CLL or NHL patients, had treatment with a short course of corticosteroids for symptom relief within 1-week prior to screening.
• Had alemtuzumab therapy within 12-weeks prior to screening.
• For AML patients, had treatment with hydroxyurea within 1-week prior to screening.
• Is pregnant or nursing.
• Has significant, ongoing co-morbid conditions which would preclude safe delivery of the study drug.
• Has had a transplant with current active graft-versus-host-disease.
• Has known active central nervous system involvement of the malignancy.
• Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
• Has significant renal or liver dysfunction.
• Has severe thrombocytopenia requiring platelet transfusion support, unless the diagnosis is AML.
• Has a positive test for human immunodeficiency virus (HIV) antibodies.
• Has active hepatitis B or C. Patients with serologic evidence of prior exposure are eligible.
• Has poorly controlled diabetes mellitus.
• Has taken a medication that is a potent inhibitor or inducer of cytochrome P450 3A4 within 1-week prior to screening.