Brief Title
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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)
Secondary Outcome
Response rate assessed by the modified IWG criteria
Condition
B-cell Adult Acute Lymphoblastic Leukemia
Intervention
6,8-bis(benzylthio)octanoic acid
Study Arms / Comparison Groups
Treatment (CPI-613, bendamustine hydrochloride, rituximab)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1
Start Date
December 2014
Completion Date
February 2015
Primary Completion Date
February 2015
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Zanetta Lamar, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02168907
Organization ID
IRB00027759
Secondary IDs
NCI-2014-01280
Responsible Party
Sponsor
Study Sponsor
Wake Forest University Health Sciences
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Zanetta Lamar, Principal Investigator, Wake Forest University Health Sciences
Verification Date
June 2018