A Study of CPI-613 for Patients With Relapsed or Refractory Burkitt Lymphoma/Leukemia or High-Grade B-Cell Lymphoma With High-Risk Translocations

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03793140

Collaborator

City of Hope Medical Center (Other), Massachusetts General Hospital (Other), M.D. Anderson Cancer Center (Other), George Washington University (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Leukemia	Drug: CPI-613	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is an open-label multicenter, single-arm, phase II trial of CPI-613 monotherapy.This is an open-label multicenter, single-arm, phase II trial of CPI-613 monotherapy.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 31, 2018

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CPI-613 CPI-613 IV induction (Days 1-5 for first 2 Cycles [14-day cycles]), followed by CPI-613 IV maintenance (Days 1-5 for all Cycles thereafter [21-day cycles].	Drug: CPI-613 CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) Induction tx: Cycle 1 and 2: Treatment on Days 1-5 (Each cycle is 14 days). (Each Cycle is 14 days) Maintenance tx: All subsequent Cycles: Treatment with CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) on Days 1-5 (Each Cycle is 21 days)

Arm

Intervention/Treatment

Experimental: CPI-613

CPI-613 IV induction (Days 1-5 for first 2 Cycles [14-day cycles]), followed by CPI-613 IV maintenance (Days 1-5 for all Cycles thereafter [21-day cycles].

Drug: CPI-613

CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) Induction tx: Cycle 1 and 2: Treatment on Days 1-5 (Each cycle is 14 days). (Each Cycle is 14 days) Maintenance tx: All subsequent Cycles: Treatment with CPI-613 [2,500 mg/m2/day IV] over 2 hours (+/- 10 mins) on Days 1-5 (Each Cycle is 21 days)

Outcome Measures

Primary Outcome Measures

overall response rate of CPI-613 [3 years]
ORR will be defined as rate of complete response (CR) + partial response (PR) + minor response (MR) + Stable disease (SD) as determined as per the RECIL criteria. RECIL criteria for response assessment in lymphoma and/or bone marrow biopsy (depending on sites of disease as indicated by treating physician).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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

Patients with active graft-versus-host-disease are not eligible
Patients receiving immunosuppressive therapy for prevention of graft-versus-host disease are not eligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
4	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
5	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
6	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
7	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
8	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
9	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553
10	Md Anderson Cancer Center	Houston	Texas	United States	77030