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 Phase II Clinical Trial of CPI-613 in Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-grade B-cell Lymphoma With Rearrangements of MYC and BCL2 and/or BCL6

The purpose of this study is to test any good and bad effects of the study drug, CPI-613.

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 DHL/THL.

• ECOG Performance Status of ≤ 3.

  1. For patients less than 16 years of age, Lansky score ≥ 30
  2. For patients 16- 17 years of age, Karnofsky score ≥ 30

• 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)]
  • 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 GFR calculation
  • 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