| Eligibility |
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
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