The purpose of this study is to determine the dose that can be safely given to see what effect it may have on your cancer and to determine how the drug is distributed in the body.

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:

1. Age > or = 18.

2. 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).

3. 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.

4. WHO performance status of ≤ 2.

5. 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.

6. Is able to provide written informed consent.

Exclusion Criteria:

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