Clinical trial NCT02168907: CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Official title: Phase I Dose-Escalation Study of CPI-613, in Combination With Bendamustine and Rituximab, in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: B-cell Adult Acute Lymphoblastic Leukemia
B-cell Chronic Lymphocytic Leukemia
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Waldenström Macroglobulinemia
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-06-20
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial studies the side effects and best dose of CPI-613 (6,8-bis\[benzylthio\]octanoic acid) when given together with bendamustine hydrochloride and rituximab in treating patients with B-cell non-Hodgkin lymphoma that has come back or has not responded to treatment. Drugs used in chemotherapy, such as 6,8-bis(benzylthio)octanoic acid and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as rituximab, may find cancer cells and help kill them. Giving 6,8-bis(benzylthio)octanoic acid with bendamustine hydrochloride and rituximab may kill more cancer cells.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of CPI-613, when used in combination with bendamustine (bendamustine hydrochloride) and rituximab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), who have or have not received hematopoietic cell transplant.

SECONDARY OBJECTIVES:

I. To evaluate response rate (RR) and disease control rate (DCR), derived from the modified International Work Group (IWG) criteria.

II. To evaluate overall survival (OS) and progression-free-survival (PFS), and possible correlation between RR and DCR derived from the modified IWG criteria vs. OS and PFS.

III. To evaluate assessment of bone marrow biopsy, and possible correlation between complete response (CR) vs. bone marrow biopsy assessment (e.g., clear of infiltration of leukemic cells accordingly to morphology, and/or negative on leukemic cells according to immunohistochemistry).

IV. To evaluate safety of the CPI-613 + bendamustine + rituximab combination.

OUTLINE: This is a dose-escalation study of 6,8-bis(benzylthio)octanoic acid.

Patients receive 6,8-bis(benzylthio)octanoic acid intravenously (IV) over 2 hours on days 1-4 (week 1) and days 1 and 4 (weeks 2 and 3). Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 and rituximab on day 5 of week 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Eligibility criteria: Inclusion Criteria:

* Histologically and cytologically confirmed B-cell NHL that has relapsed from, or is refractory to, all standard therapies (including autologous transplantation) known to provide clinical benefit, but have not been treated with bendamustine for their lymphoma
* Must have measurable disease (e.g., a tumor mass \> 1 cm)
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Expected survival \> 3 months
* 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 1 week prior to treatment initiation
* Fertile men must practice effective contraceptive methods during the study, unless documentation of infertility exists
* At least 2 weeks must have elapsed from any prior surgery
* Aspartate aminotransferase (AST/serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT/serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x upper normal limit (UNL) (=\< 5 x UNL if liver metastases present)
* Bilirubin =\< 1.5 x UNL
* Serum creatinine =\< 1.5 mg/dL or 133 umol/L
* "International normalized ratio" or INR must be =\< 1.5
* No evidence of active infection and no serious infection within the past month
* Mentally competent, ability to understand and willingness to sign the informed consent form

Exclusion Criteria:

* Known cerebral metastases, central nervous system (CNS) or epidural tumor
* Having "currently active" second malignancy unrelated to Hodgkin lymphoma (HL) or NHL, unless they have completed anti-cancer therapy, are in complete response and are considered by their physicians to be at less than 30% risk of relapse
* Patients receiving any other standard or investigational treatment for their cancer, or any other investigational agent for any indication, within the past 2 weeks prior to initiation of treatment with study drugs
* Serious medical illness that would potentially increase patients' risk for toxicity
* Any active uncontrolled bleeding, and any patients with a bleeding diathesis (e.g., active peptic ulcer disease)
* History of abdominal fistula or gastrointestinal perforation =\< 6 months prior to treatment with study drugs
* Pregnant women, or women of child-bearing potential not using reliable means of contraception
* Lactating females
* Fertile men unwilling to practice contraceptive methods during the study period
* Any condition or abnormality which may, in the opinion of the investigator, compromise the safety of patients
* Unwilling or unable to follow protocol requirements
* Active heart disease including but not limited to symptomatic congestive heart failure, symptomatic coronary artery disease, symptomatic angina pectoris, symptomatic myocardial infarction or symptomatic congestive heart failure
* Patients with a history of myocardial infarction that is \< 3 months prior to registration
* Evidence of active infection, or serious infection within the past month
* Patients with known human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C
* Patients who have received cancer immunotherapy of any type within the past 2 weeks prior to initiation of CPI-613 treatment
* Requirement for immediate palliative treatment of any kind including surgery

Primary outcomes:
measure: MTD of 6,8-bis(benzylthio)octanoic acid, when used in combination with bendamustine hydrochloride and rituximab determined by dose-limiting toxicities graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: 4 weeks
Secondary outcomes:
measure: Response rate assessed by the modified IWG criteria
timeFrame: Up to 2 years
measure: Disease control rate assessed by the modified IWG criteria
timeFrame: Up to 2 years
measure: Overall survival assessed by the modified IWG criteria
timeFrame: Up to 2 years
measure: Progression free survival assessed by the modified IWG criteria
timeFrame: Up to 2 years
measure: Bone marrow biopsy analysis
timeFrame: Baseline
measure: Incidence of toxicities graded according to NCI CTCAE
timeFrame: Up to 6 courses
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Zanetta Lamar
role: PRINCIPAL_INVESTIGATOR
References: