| Eligibility |
Inclusion Criteria:
1. Age 18-65
2. Patients with:
2.1 Diffuse large B-cell lymphoma (DLBCL) with one of the following: 2.1.1 Primary
refractory (no CR to 1st line) 2.1.2 High-risk relapse, defined as any of the
following: CR1 <6 mo, secondary IPI >1, or LDH > 225 U/L. 2.1.3 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.
2.2 Hodgkin's with one of the following: 2.2.1 Primary refractory (no CR or PD within
3 months) 2.2.2 High-risk relapse, defined as any of the following: CR1 <1 year,
extranodal relapse, or B symptoms.
2.2.3 Refractory relapse: No response to >/= 1 salvage line 2.3 T-non Hodgkin's
lymphoma (T-NHL) with one of the following: 2.3.1 Primary refractory (no CR to 1st
line) 2.3.2 High-risk relapse (within 6 months) 2.3.3 Refractory relapse to >/= 1 line
of salvage 2.3.4 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)) </= 3.5 x institutional upper limit of normal unless
liver metastases or a systemic inflammatory picture secondary to the lymphoma are
present in which case they must be </= 6x ULN; total bilirubin </= 2.5 x ULN or </=
3.5 x ULN if Gilbert's disease)
5. Prothrombin time (PT) </=1.5 x institutional upper limit of normal
6. Adequate pulmonary function (FEV1, FVC and DLCOc >/= 50% of predicted)
7. Adequate cardiac function (LVEF >/= 40%, no uncontrolled arrhythmias or symptomatic
cardiac disease
8. ECOG performance status <2
9. Provision of informed consent prior to any study specific procedures
10. Patients must have a life expectancy >/= 16 weeks
11. 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 one
of the following:
11.1 Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments.
11.2 Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the
postmenopausal range for women under 50.
11.3 Radiation-induced oophorectomy with last menses >1 year ago. 11.4
Chemotherapy-induced menopause with >1 year interval since last menses. 11.5 Surgical
sterilization (bilateral oophorectomy or hysterectomy). 11.6 Female patients must
agree to use a highly effective birth control method while on study and for at least 6
months after the last dose of study drug(s).
12. 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 6 months after
last dose of study drug(s) to prevent pregnancy in a partner.
13. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations.
14. Prior apheresis of >/= 3 million CD34+ cells/Kg.
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 QTcF > 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.
20. Medical, psychiatric, cognitive or other conditions that compromise the patient's
ability to understand the patient information, to give informed consent, to comply
with the study protocol or to complete the study.
|
