CPI-613 in Treating Patients with Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-cell Lymphoma with MYC, BCL2, and/or BCL6 Gene Rearrangements

Inclusion Criteria

• Must be >= 12 years of age
• 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 or plasmablastic lymphoma or high-grade B-cell lymphoma with rearrangements of MYC without bcl-2
• Failure of at least one previous line of therapy
• Failure after prior bone marrow transplant, or ineligible for or opted not to participate in bone marrow transplantation for Burkitt lymphoma/leukemia, or double hit lymphoma (DHL)/triple hit lymphoma (THL)
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 * For patients less than 16 years of age, Lansky score >= 30 * For patients 16- 17 years of age, Karnofsky score >= 30
• Measurable disease as defined Response Evaluation Criteria in Lymphoma (RECIL) criteria (2017) or isolated bone marrow involvement
• Patients must have fully recovered from the acute, non-hematological, noninfectious 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
• Patients must have, or be willing and eligible to undergo placement of, a working central venous access device
• Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) =< 5 x upper normal limit (ULN) (obtained =< 2 weeks prior to enrollment)
• Alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 5 x ULN (obtained =< 2 weeks prior to enrollment)
• Total bilirubin =< 1.5 x ULN (unless related to hemolysis, Gilbert’s syndrome, or involvement by lymphoma; if involvement by lymphoma: total bilirubin =< 3.0 x ULN) (obtained =< 2 weeks prior to enrollment)
• Creatinine clearance >= 40 cc min either by 24-hour creatinine clearance or calculated from the modified Cockcroft-Gault equation (obtained =< 2 weeks prior to enrollment) * For patients less than 16 years of age, the Bedside Schwartz equation or Creatinine-Cystatin C-based CKiD equation should be used for creatinine-based glomerular filtration rate (GFR) calculation
• International normalized ratio (INR) must be < 1.5 (obtained =< 2 weeks prior to enrollment). 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) (obtained =< 2 weeks prior to enrollment)
• 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
• Females must agree to abstain from breastfeeding during study participation
• Fertile men must practice effective contraceptive methods during the study unless documentation of infertility exists

Exclusion Criteria

• Patients that have received a chemotherapy regimen with stem cell support in the previous 2 months
• Any medical condition that is clinically unstable despite present therapy (i.e. uncontrolled infection)
• Platelets < 50,000/mm^3 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
• 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
• Patients with active central nervous system (CNS) parenchymal disease. Patients with leptomeningeal disease are allowed as long as the cerebrospinal fluid (CSF) has cleared for more than 4 weeks and the patient is receiving maintenance intrathecal/intra Ommaya therapy
• Any active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease)
• Any condition or abnormality which may, in the opinion of the investigator, compromise his or her safety
• Human immunodeficiency virus (HIV) patients with any of the following: uncontrolled HIV infection defined as an HIV viral load > 100K copies/mL, a documented opportunistic infection within the last 90 days, 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
• 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, with the exclusion of radiation to one area (eg. whole brain or involved nodal site) that does not interfere with response assessment in other sites. A course of steroids (up to 14 days total) prior to study initiation is acceptable
• Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements
• Prior allogeneic stem cell transplant within 2 months of study start * Patients with active graft-versus-host-disease are not eligible * Patients receiving immunosuppressive therapy for prevention of graft-versus-host disease are not eligible