Olaparib Combined With High-Dose Chemotherapy for Refractory Lymphomas

Busulfan Test Dose:

You will receive a test dose of busulfan by vein over about 60 minutes. Before and after you
receive this low-level test dose of busulfan, blood will be drawn several times to check how
the level of busulfan in your blood changes over time. This is called pharmacokinetic (PK)
testing. This information will be used to decide the next dose needed to reach the correct
blood level that matches your body size. You will most likely receive this test dose as an
outpatient during the week before you are admitted to the hospital. If it cannot be given as
an outpatient, you will be admitted to the hospital on Day -13 (13 days before your stem
cells are returned to your body) and the test dose will be given on Day -12.

Blood (about 1 teaspoon each time) will be drawn for PK testing about 11 times: once before
your test dose of busulfan and 10 times over the 11 hours after the dose. The blood samples
will be repeated again on the first day of high-dose busulfan treatment (Day -9). A temporary
heparin lock line will be placed in your vein to lower the number of needle sticks needed for
these draws.

If it is not possible for the PK tests to be performed for any reason, you will receive the
standard fixed dose of busulfan.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a dose
level of olaparib based on when you join this study. Up to 8 dose levels will be tested.
Between 3-6 participants will be enrolled at each dose level. The first group of participants
will receive the lowest dose level. Each new group will receive a higher dose than the group
before it, if no intolerable side effects were seen. This will continue until the highest
tolerable dose of olaparib is found.

All participants will receive the same dose level of vorinostat, melphalan, and rituximab
(for those who receive it). The first participants enrolled on this study may receive a lower
dose of gemcitabine, but all other participants will receive the same dose level of
gemcitabine.

Study Drug Administration:

Starting 2 days before you are admitted to the hospital and on the day you are admitted, you
will receive palifermin by vein over about 30 seconds each day to help decrease the side
effects in the mouth and throat.

On Day -11 through Day -3, you will take olaparib by mouth 2 times a day, about 12 hours
apart, with or without food, with a glass of water. The olaparib tablets should be swallowed
whole and not chewed, crushed, dissolved, or divided. Olaparib tablets can be taken with or
without food.

If you vomit after taking your olaparib dose, but you can see all the tablets are intact, you
should retake that dose. If you miss or vomit a scheduled dose, you should take the scheduled
dose up to 2 hours after that scheduled dose time. If more than 2 hours after the scheduled
dose time, the missed dose should not to be taken and you should wait and take your next
scheduled dose.

On Day -10 through -3, you will take vorinostat by mouth. The study staff will tell you how
many olaparib and vorinostat tablets to take. You will also receive dexamethasone by vein
over about 3-5 minutes 2 times each day. Dexamethasone is a standard drug given to help
decrease the risk of certain side effects.

On Day -10, if you have a type of B-cell cancer, you will receive rituximab (a treatment used
for certain lymphomas) by vein over about 3-6 hours as part of your standard care. The study
doctor will tell you if you will receive rituximab.

On Day -9, you will receive gemcitabine by vein over 4½ hours.

On Days -9, -8, -7, and -6, you will receive busulfan by vein over about 3 hours.

On Day -4, you will receive gemcitabine by vein over 4½ hours and then melphalan by vein over
30 minutes.

On Day -3, you will receive melphalan by vein over 30 minutes.

On Days -2 and -1, you will rest (you will not receive chemotherapy).

On Day 0, you will receive your stem cells by vein over about 30-60 minutes.

You will receive 3 more doses of palifermin by vein, over about 30 seconds each time, on Days
0, +1, and +2.

As part of standard care, you will receive G-CSF (filgrastim) as an injection just under your
skin 1 time each day starting on Day +5 until your blood cell levels return to normal. The
study doctor will discuss this with you, including how filgrastim is given and its risks.

You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff for information about how the drugs are given and their risks.

Length of Study:

You will be taken off study about 100 days after the transplant. You may be taken off study
earlier if the disease gets worse, if intolerable side effects occur, or if you are unable to
follow study directions.

Study Tests:

Within 7 days before starting study treatment, you will have an EKG to check your heart
function. This may be repeated during the study, if your doctor thinks it is needed.

As part of your standard care, you will remain in the hospital for about 3-4 weeks after the
transplant. While you are in the hospital, blood (about 4 teaspoons) will be drawn every 1-2
days for routine tests. After you are released from the hospital until about 30 days after
the transplant, you will need to stay in the Houston area to be checked for infections and
side effects.

Between discharge and Day 30, you will come to the clinic every 1 to 2 days for standard
follow-up visits. The results of these routine tests will also be included in your study
record.

Between Days 30 and 100 after the transplant, you will come to the clinic about every 2 weeks
for standard follow-up visits. The results of these routine tests will also be included in
your study record. Every 2 weeks, or more often if your doctor thinks it is needed, blood
(about 2 teaspoons) will be drawn for routine tests. These blood tests may instead be
performed by your personal doctor, as long as they agree to provide care as part of this
study.

About 100 days after the transplant:

- You will have a physical exam.

- Blood (about 4 teaspoons) and urine will be collected for routine tests.

- If the doctor thinks it is needed, you may have a bone marrow aspiration and biopsy to
check the status of the disease. To collect a bone marrow aspiration/biopsy, an area of
the hip is numbed with anesthetic, and a small amount of bone marrow and bone is
withdrawn through a large needle.

Inclusion Criteria:

1. Age 18-65

2. Patients with: A) Diffuse large B-cell lymphoma (DLBCL) with one of the following:
A.1) Primary refractory (no CR to 1st line), A.2) High-risk relapse (CR1 <6 mo,
secondary IPI >1, high LDH), A.3) Refractory relapse: No response to >/= 1 salvage
line and not eligible to receive other novel salvage therapies, such as CAR-T in a
timely fashion or have already failed these; B) Hodgkin's with one of the following:
B.1) Primary refractory (no CR or PD within 3 months), B.2) High-risk relapse (CR1 <1
year, extranodal relapse, B symptoms), B.3) Refractory relapse: No response to >/= 1
salvage line C) T-non Hodgkin's lymphoma (T-NHL) with one of the following: C.1)
Primary refractory (no CR to 1st line), C.2) High-risk relapse (within 6 months), C.3)
Refractory relapse to >/= 1 line of salvage. D) Any other lymphoma that is refractory
or relapsed and that does not qualify for autologous transplant protocols of higher
priority.

3. Adequate renal function (creatinine clearance estimated using the Cockcroft-Gault
equation of >/= 51 mL/min: Estimated creatinine clearance = (140-age [years]) x weight
(kg) (xF)a / serum creatinine (mg/dL) x 72 [a where F=0.85 for females and F=1 for
males.]

4. Adequate hepatic function (Aspartate aminotransferase (AST) (Serum Glutamic
Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic
Pyruvate Transaminase (SGPT)) liver metastases are present in which case they must be
5. Adequate pulmonary function (FEV1, FVC and DLCOc >/= 50% of predicted)

6. Adequate cardiac function (LVEF >/= 40%, no uncontrolled arrhythmias or symptomatic
cardiac disease

7. ECOG performance status <2

8. Provision of informed consent prior to any study specific procedures

9. Patients must have a life expectancy >/= 16 weeks

10. Postmenopausal or evidence of non-childbearing status for women of childbearing
potential: negative urine or serum pregnancy test within 28 days and within 72 hours
of study treatment and confirmed prior to receiving treatment on this study. Patients
with positive results will be removed from the study. Postmenopausal is defined as: 1.
Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
2. Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the
postmenopausal range for women under 50. 3. Radiation-induced oophorectomy with last
menses >1 year ago. 4. Chemotherapy-induced menopause with >1 year interval since last
menses. 5. Surgical sterilization (bilateral oophorectomy or hysterectomy). 6. Female
patients must agree to use a highly effective birth control method while on study and
for at least 1 month after your last dose of study drug(s).

11. Male patients and their partners, who are sexually active and of childbearing
potential, must agree to the use of two highly effective forms of contraception in
combination, throughout the period of taking study treatment and for 3 months after
last dose of study drug(s) to prevent pregnancy in a partner.

12. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations.

13. Prior apheresis of >/= 3 million CD34+ cells/Kg.

14. Eligibility for ASCT is determined by the above inclusion criteria 3-7.

Exclusion Criteria:

1. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2)
caused by previous cancer therapy, excluding alopecia.

2. Prior whole brain irradiation

3. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA >/= 10,000
copies/mL, or >/= 2,000 IU/mL)

4. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic
hepatitis C or positive hepatitis C serology

5. Active infection requiring parenteral antibiotics

6. Patients who are known to be serologically positive for human immunodeficiency virus
(HIV).

7. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative
reasons) within 3 weeks prior to study treatment.

8. Pregnancy

9. Other malignancy within the last 5 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ
(DCIS), Stage 1, grade 1 endometrial carcinoma, or other solid tumors.

10. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or
family history of long QT syndrome.

11. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin,
clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,
saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg.
ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout
period prior to starting olaparib is 2 weeks.

12. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin,
rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort ) or
moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout
period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3
weeks for other agents.

13. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features
suggestive of MDS/AML.

14. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence
of brain metastases is not required. The patient can receive a stable dose of
corticosteroids before and during the study as long as these were started at least 4
weeks prior to treatment. Patients with spinal cord compression unless considered to
have received definitive treatment for this and evidence of clinically stable disease
for 28 days.

15. Major surgery within 2 weeks of starting study treatment and patients must have
recovered from any effects of any major surgery.

16. Uncontrolled non-malignant systemic disease or active, uncontrolled infection.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent
(within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable
spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral
lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric
disorder that prohibits obtaining informed consent.

17. Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication.

18. Breast feeding women.

19. Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.