Clinical trial NCT03793140: A Study of CPI-613 for Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma With High-Risk Translocations
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma
Leukemia
Keywords: Burkitt Lymphoma/Leukemia
high-grade B-cell lymphoma
CPI-613
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: City of Hope Medical Center
name: Massachusetts General Hospital
name: M.D. Anderson Cancer Center
name: George Washington University
First posted: 2019-01-04
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label multicenter, single-arm, phase II trial of CPI-613 monotherapy.
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: overall response rate of CPI-613
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania (Data Collection Only)
state: Pennsylvania
city: Houston
country: United States
facility: Md Anderson Cancer Center
state: Texas
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ariela Noy, MD
role: PRINCIPAL_INVESTIGATOR
References: