- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02168907
CPI-613, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
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 Overview
Status
Conditions
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell Lymphoma
- 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 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
- Splenic Marginal Zone Lymphoma
- Waldenström Macroglobulinemia
- Cutaneous B-cell Non-Hodgkin Lymphoma
- Intraocular Lymphoma
- Recurrent Adult Acute Lymphoblastic Leukemia
- Recurrent Adult Grade III Lymphomatoid Granulomatosis
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Small Lymphocytic Lymphoma
- Small Intestine Lymphoma
- Testicular Lymphoma
- B-cell Chronic Lymphocytic Leukemia
- Refractory Chronic Lymphocytic Leukemia
- B-cell Adult Acute Lymphoblastic Leukemia
- Refractory Hairy Cell Leukemia
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Comprehensive Cancer Center of Wake Forest University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (CPI-613, bendamustine hydrochloride, rituximab)
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.
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Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
Time Frame: 4 weeks
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Will be accomplished by monitoring toxicities and using the dose escalation plan.
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4 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate assessed by the modified IWG criteria
Time Frame: Up to 2 years
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The response rate and its 95% confidence interval will be assessed.
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Up to 2 years
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Disease control rate assessed by the modified IWG criteria
Time Frame: Up to 2 years
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The DCR and its 95% confidence interval will be assessed.
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Up to 2 years
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Overall survival assessed by the modified IWG criteria
Time Frame: Up to 2 years
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OS curves will be plotted using Kaplan-Meier methods.
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Up to 2 years
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Progression free survival assessed by the modified IWG criteria
Time Frame: Up to 2 years
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PFS curves will be plotted using Kaplan-Meier methods and median PFS will be examined.
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Up to 2 years
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Bone marrow biopsy analysis
Time Frame: Baseline
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Evaluation of bone marrow and possible correlation between CR vs. bone marrow biopsy assessments such as clear of infiltration of leukemic cells accordingly to morphology, and/or negative on leukemic cells according to immunohistochemistry. Correlations will be estimated to examine the relationship between results from bone marrow biopsies and response and time to event results.
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Baseline
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Incidence of toxicities graded according to NCI CTCAE
Time Frame: Up to 6 courses
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Will be examined by looking at each toxicity identified earlier in the protocol by grade.
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Up to 6 courses
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Zanetta Lamar, Wake Forest University Health Sciences
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Bacterial Infections and Mycoses
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Precancerous Conditions
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Eye Neoplasms
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Leukemia
- Recurrence
- Lymphoma, Non-Hodgkin
- Mycoses
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
- Mycosis Fungoides
- Sezary Syndrome
- Lymphomatoid Granulomatosis
- Intraocular Lymphoma
- Leukemia, Hairy Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Immunological
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin B Complex
- Bendamustine Hydrochloride
- Rituximab
- Thioctic Acid
Other Study ID Numbers
- IRB00027759
- P30CA012197 (U.S. NIH Grant/Contract)
- NCI-2014-01280 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- CCCWFU 28114 (OTHER: Comprehensive Cancer Center of Wake Forest University)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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