a study of cpi-613 for patients with relapsed or refractory burkitt lymphoma/leukemia or high-grade b-cell lymphoma with high-risk translocations

Conditions: Lymphoma; Leukemia

Summary: the purpose of this study is to test any good and bad effects of the study drug, cpi-613.


Eligibility criteria:
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

Keywords: burkitt lymphoma/leukemia high-grade b-cell lymphoma cpi-613