Idelalisib Post Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in B Cell Derived Malignancies

Currently, to improve overall survival, the focus of the BMT program at JHH the introduction
of anti-neoplastic therapy post transplantation: where the allo BMT serves as a platform to
allowing a new intolerant immune system to interact with the post allo BMT intervention.

The importance of post BMT therapy has been made evident with tyrosine kinase inhibition
(TKI) in Philadelphia chromosome positive acute lymphocytic leukemia (ALL) and chronic
myeloid leukemia(CML), where patients who had disease progression while on TKI therapy
pre-allo BMT enjoy marked improvement in overall survival when TKI is part of a maintenance
program; the use of DNA hypomethylation agents after allo BMT for relapsed myeloid
malignances; or the use of rituximab after allo BMT in follicular lymphoma.

Idelalisib, an orally-administered, selective inhibitor of Phosphoinositide 3 kinase (PI3K),
is extremely effective in inducing partial responses to complete responses in many B-cell
derived malignancies and should be studied in the post alloHSCT setting. Johns Hopkins
Hospital has one of the world's largest experiences with alloHSCT. This study proposes a
double blinded randomized phase I placebo trial where all patients who have undergone
alloHSCT for a B-cell derived hematologic malignancy be offered either idelalisib 100mg or
placebo twice daily for 180 days starting approximately 90 days after their HSCT.

INCLUSION CRITERIA

1. >18 years of age

2. Has undergone allo HSCT to treat a B-cell derived hematologic malignancy: accepted
alloHSCT regimens include: myeloablative or reduced intensity conditioning from any
donor (matched, partially mismatched or cord) and any source (peripheral blood, bone
marrow, or cord).

3. T bili ≤ 1.5 mg/dL except for patients with Gilbert's syndrome or hemolysis

4. AST, ALT and alk phos all < 2.5X ULN

5. Karnofsky performance score ≥ 40

6. ECOG ≤3

7. For women of childbearing potential, a negative serum or urine pregnancy test with
sensitivity less than 50 mIU/m within 72 hours before the start of study medication.

8. Use of two forms of contraception with less than a 5% failure rate or abstinence by
all transplanted patients for a minimum of 1 month after the last dose of Idelalisib.
For the first 60 days post-transplant, transplant recipients should be encouraged to
use non-hormonal contraceptives due to the potential adverse effect of hormones on
bone marrow engraftment.

9. Ability to receive oral medication.

10. Ability to understand and provide informed consent.

EXCLUSION CRITERIA

1. ECOG >3 (Karnofsky <40%)

2. ALT, AST >2.5 ULN or total bilirubin >1.5 ULN (not attributable to Gilbert's)

3. Women who are pregnant or breastfeeding.

4. Exclude if patient has cirrhosis or is currently being actively treated for hepatitis
C.

5. History of positive HIV-1 or HIV-2 serologies or nucleic acid test.

6. Active hepatitis B infection as documented by positive Hepatitis B PCR assay

7. Use of investigational drug, other than the study medications specified by the
protocol, within 30 days of transplantation.

8. Receipt of a live vaccine within 30 days of receipt of study therapy.

9. ≥ Grade II aGVHD

10. The presence of any medical condition that the Investigator deems incompatible with
participation in the trial

11. Subjects who are required to use a medication classified as a strong CYP3A inducer of
inhibitor.