A Study of CPI-613 for Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma With High-Risk Translocations
A Study of CPI-613 for Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma With High-Risk Translocations
The purpose of this study is to test any good and bad effects of the study drug, CPI-613.
Inclusion Criteria:

 -  Must be ≥ 18 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

 -  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 DHL/THL.

 -  ECOG Performance Status of ≤ 3.

 -  Measurable disease as defined RECIL criteria (2017) or isolated bone marrow
 involvement.

 -  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.

 -  Patients must have, or be willing and eligible to undergo placement of, a working
 central venous access device

 -  Venous access available (e.g., portacath, PICC line or equivalent).

 -  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, or
 involvement by lymphoma; if involvement by lymphoma: total bilirubin </= 3.0 x
 ULN)

 -  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)

 -  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/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.

 -  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 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.

 -  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.

 -  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 (e.g. 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

 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