Clinical Trial 18-443: Patients with Burkitt’s Lymphoma/Leukemia or High-Grade B-cell Lymphoma

Inclusion

1. Must be ≥ 18 years of age.
2. Histologic diagnosis of Burkitt Lymphoma/Leukemia or high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 confirmed at enrolling institution
3. Failure of at least one previous line of therapy.
4. Failure after prior bone marrow transplant, or ineligible for or opted not to participate in bone marrow transplantation for Burkitt Lymphoma/Leukemia, or DHL/THL.
5. ECOG Performance Status of ≤ 3.
6. Measurable disease as defined RECIL criteria (2017) or isolated bone marrow involvement.
7. Patients must have fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with anti-cancer drugs, radiotherapy or other anti-cancer modalities. Patients with persistent, non-hematologic, non-infectious toxicities from prior treatment must have documented resolution to ≤ Grade 2.
8. Central venous access available (e.g., portacath, PICC line or equivalent).
9. Laboratory values obtained ≤ 2 weeks prior to enrollment must demonstrate adequate hepatic function, renal function, and coagulation as defined below:
   Aspartate aminotransferase (AST/SGOT) ≤ 5x upper normal limit (ULN)
   Alanine aminotransferase (ALT/SGPT) ≤ 5x ULN Total bilirubin ≤1.5x ULN (unless related to hemolysis or Gilbert‘s syndrome) Creatinine clearance >=40cc min either by 24-hour creatinine clearance or calculated from the modified Cockcroft-Gault equation (with the use of ideal body mass [IBM] instead of mass): CRCL =(140−Age) × IBM (kg) × [0.85 if female]/[(72 • serum creatinine (mg/dL)] International Normalized Ratio (INR) must be <1.5. Due to the occurrence of thrombocytopenia, patients should not enter with coagulopathy. Patients on anticoagulants should be on short-acting therapy (e.g. low molecular weight heparin) rather than oral anticoagulants. Albumin ≥2.0 g/dL (or ≥20 g/L)
10. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must use accepted contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) during the study and must have a negative serum or urine pregnancy test within 2 weeks prior to treatment initiation.
11. Females must agree to abstain from breastfeeding during study participation
12. Fertile men must practice effective contraceptive methods during the study unless documentation of infertility exists.
13. Patients must have, or be willing and eligible to undergo placement of, a working central venous access device.

Exclusion

1. Patients that have received a chemotherapy regimen with stem cell support in the previous 3 months.
2. Any medical condition that is clinically unstable despite present therapy (i.e. uncontrolled infection).
3. Platelets < 50,000/mm³ unless attributable to marrow based (either Burkitt lymphoma or DHL/THL.) Note: Patients with leukemia/lymphoma in the marrow 25,000-50,000 will be assessed for grade 4 thrombocytopenia unless they have platelet recovery above grade 3. Patients entering with platelets <25,000 will only be assessed for thrombocytopenia related to drug if they recover to grade 3 or higher.
4. Serious medical illness, such as significant cardiac disease (e.g. symptomatic congestive heart failure, unstable angina pectoris, coronary artery disease, myocardial infarction within the past 3 months, uncontrolled cardiac arrhythmia, pericardial disease or New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patient‘s risk for toxicity.
5. Patients with active central nervous system (CNS) parenchymal disease. Patients with leptomeningeal disease are allowed as long as the CSF has cleared for more than 4 weeks and the patient is receiving maintenance intrathecal/intra Ommaya therapy.
6. Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
7. Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety.
8. Life expectancy less than 2 months.
9. Requirement for immediate palliative treatment of any kind including surgery.
10. HIV patients with any of the following: a) uncontrolled HIV infection defined as an HIV viral load > 100K copies/mL, b) a documented opportunistic infection within the last 90 days, c) concurrent HIV therapy with zidovudine or any strong CYP3A4 inhibitor (e.g. ritonavir or cobicistat) within 7 days of study drug due to potential drug-drug interaction.
11. Patients who have received radiotherapy, surgery, treatment with cytotoxic agents, treatment with biologic agents, immunotherapy, or any other anti-cancer therapy for any kind for cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of CPI-613^® treatment.
12. Psychiatric illness or social situation that would limit the patient’s ability to tolerate and/or comply with study requirements.
13. Prior allogeneic stem cell transplant within 2 months of study start
    1. Patients with active graft-versus-host-disease are not eligible
    2. Patients receiving immunosuppressive therapy for prevention of graft-versus-host disease are not eligible