This is a pilot study to learn how safe and how effective the study drug Zydelig works, after autologous stem cell transplant as a maintenance therapy in patients with indolent or transformed indolent B-cell non-Hodgkins lymphoma (iNHL or tiNHL).

This pilot study is focused on maintenance Zydelig for patients with indolent or transformed indolent B-cell non-Hodgkins lymphoma (iNHL or tiNHL) after autologous stem cell transplantation. Oral Zydelig at 150 mg (or adjusted dose) twice daily continuously on 28-day cycles. Patients will continue on Zydelig up to one year or to progression/relapse/death or unacceptable toxicity, whichever occurs first.

Inclusion Criteria:

1. Histologically documented (by HPI or pathology report) iNHL as defined by follicular lymphoma (FL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma/Waldenstrom disease (LPL/WM) and small lymphocytic lymphoma (SLL) or tiNHL as defined by large B cell transformation of any of the above entities including chronic lymphocytic leukemia (CLL)

2. Patients must be eligible to undergo high dose chemotherapy (HDT) followed by ASCT as a form of remission consolidation

3. Patients without evidence of documented disease progression clinically or radiographically after ASCT (stable disease (SD), partial remission (PR) or complete remission (CR)) who have had count recovery (ANC > 500, non-transfused platelet count > 20,000) and are at least 30 days post ASCT but no more than 120 days post ASCT

4. Patients may have received any prior therapy deemed necessary for them to be eligible to HDT/ASCT except for patients whom have progressed while on Zydelig. Patients who have responded to Zydelig previously are eligible for enrollment on the protocol.

5. Age >18

6. ECOG performance status <4

7. Life expectancy of greater than four months.

8. Patients must have normal organ function as defined below (after the HDT/ASCT):

   • total bilirubin less than 2x institutional upper limit of normal
   • AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
   • Creatinine < 1.5x institutional upper limit of normal OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels > 1.5x upper limit of normal.

9. Because the effects of Zydelig on the developing human fetus are unknown, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Participants must agree to use contraception for at least 30 days after the last dose of Zydelig. Women of childbearing potential is defined as women who continues to have menstrual periods, have not had a tubal ligation, or the removal of fallopian tubes, ovaries or uterus.

10. Ability to understand English and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients who have had chemotherapy or radiotherapy within 2 weeks of first dose of Zydelig.

2. Patients receiving any other investigational agents within 30 days of receiving Zydelig

3. Patients who were previously exposed to Zydelig and experienced progression of disease.

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Zydelig.

5. Patients with active and/or untreated CNS lymphoma will not be eligible.

6. Patients with inflammatory bowel disease.

7. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (defined as requiring systemic antibiotic treatment and fever within 48 hours of screening), symptomatic congestive heart failure (patients with NYHA score of III and above are excluded), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

8. Women who are pregnant or nursing or plan to become pregnant or nurse during the course of the study.

9. Positive HIV status.

10. Patients with lack of count recovery as defined in Protocol 3.1.1.1.1.

11. Patients who are unable to swallow pills.

12. Patients with moderate to severe lung disease including:

    • Patients requiring O2 supplementation
    • Patients unable to walk 50 feet without stopping to rest
    • Moderate to severe obstructive or restrictive disease of the lung

13. Patients taking strong CYP3A4 inhibitors or inducers with Risk X (Avoid Combination) according to Lexicomp. Please see appendix C of the protocol for more information.

14. Patients with active hepatic disease, liver cirrhosis, or known HBV/HCV infection.

15. Patients with de novo diffuse large B-cell lymphoma.

16. Patients with h/o PCP pneumonia or CMV infection.