CPI-613 and Bendamustine Hydrochloride in Treating Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Hodgkin Lymphoma

Phase I Dose-Escalation Study of CPI-613, in Combination With Bendamustine, in Patients With Relapsed or Refractory T-Cell Non-Hodgkin Lymphoma or Classic Hodgkin Lymphoma

This phase I trial studies the side effects and best dose of CPI-613 when given together with bendamustine hydrochloride in treating patients with relapsed or refractory T-cell non-Hodgkin lymphoma or Hodgkin lymphoma. CPI-613 may kill cancer cells by turning off their mitochondria, which are used by cancer cells to produce energy and are the building blocks needed to make more cancer cells. By shutting off mitochondria, CPI-613 may deprive the cancer cells of energy and other supplies needed to survive and grow. Drugs used in chemotherapy, such as 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. Giving CPI-613 with bendamustine hydrochloride may kill more cancer cells.

Study Overview

• Status: Completed
• Conditions: Peripheral T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Noncutaneous Extranodal Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma
• Intervention / Treatment: Drug: bendamustine hydrochloride; Drug: 6,8-bis(benzylthio)octanoic acid

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of CPI-613 [6,8-bis(benzylthio)octanoic acid], when used in combination with bendamustine (bendamustine hydrochloride) in patients with relapsed and refractory classic Hodgkin lymphoma (HL) or T-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 and International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphomas.

II. To evaluate overall survival (OS) and progression-free survival (PFS), and possible correlation between RR and DCR derived from modified IWF 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 according to morphology, and/or negative on leukemic cells according to immunohistochemistry).

IV. To evaluate safety of CPI-613 + bendamustine 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 of week 1 and on days 1 and 4 of weeks 2 and 3. Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 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: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Comprehensive Cancer Center of Wake Forest University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed T-cell NHL or classic HL (i.e., nodular sclerosis HL, mixed cellularity HL, lymphocyte rich classic HL, and lymphocyte depleted HL) 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]) =< 3 x upper normal limit (UNL), alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3 x UNL (=< 5 x UNL if liver metastases present)
• Bilirubin =< 1.5 x UNL
• Serum creatinine =< 1.5 mg/dL or 133 µmol/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 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (CPI-613 and bendamustine hydrochloride); Patients receive 6,8-bis(benzylthio)octanoic acid IV over 2 hours on days 1-4 of week 1 and on days 1 and 4 of weeks 2 and 3. Patients also receive bendamustine hydrochloride IV over 30 minutes on days 4 and 5 of week 1. Treatment repeats every 4 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: bendamustine hydrochloride; Given IV; Other Names: Treanda; bendamustin hydrochloride; bendamustine; cytostasan hydrochloride; Drug: 6,8-bis(benzylthio)octanoic acid; Given IV; Other Names: CPI-613; alpha-lipoic acid analogue CPI-613

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, defined as the dose level immediately below the dose level that induced a dose-limiting toxicity in < 2 patients	Graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma	RR and its 95% confidence interval will be assessed. RR and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Up to 3 years
DCR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma	DCR and its 95% confidence interval will be assessed. DCR and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Up to 3 years
OS	OS curves will be plotted using Kaplan-Meier methods. OS and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Time from first dose of 6,8-bis(benzylthio)octanoic acid to death by any cause, assessed up to 3 years
PFS	PFS curves will be plotted using Kaplan-Meier methods and median PFS will be examined. PFS and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Time from first dose of 6,8-bis(benzylthio)octanoic acid to disease progression, assessed up to 3 years
Bone marrow biopsy assessment	Bone marrow and possible correlation between CR vs. bone marrow biopsy assessments such as clear of infiltration of leukemic cells according to morphology, and/or negative on leukemic cells according to immunohistochemistry will be evaluated.	After course 6 (168 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
RR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma	RR and its 95% confidence interval will be assessed. RR and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Up to 3 years
DCR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma	DCR and its 95% confidence interval will be assessed. DCR and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Up to 3 years
OS	OS curves will be plotted using Kaplan-Meier methods. OS and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Time from first dose of 6,8-bis(benzylthio)octanoic acid to death by any cause, assessed up to 3 years
PFS	PFS curves will be plotted using Kaplan-Meier methods and median PFS will be examined. PFS and the possible correlation between RR and DCR vs. OS and PFS will be evaluated.	Time from first dose of 6,8-bis(benzylthio)octanoic acid to disease progression, assessed up to 3 years
Bone marrow biopsy assessment	Bone marrow and possible correlation between CR vs. bone marrow biopsy assessments such as clear of infiltration of leukemic cells according to morphology, and/or negative on leukemic cells according to immunohistochemistry will be evaluated.	After course 6 (168 days)

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Rakhee Vaidya, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): April 18, 2019
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: June 18, 2014
• First Submitted That Met QC Criteria: June 18, 2014
• First Posted (Estimated): June 20, 2014

Study Record Updates

• Last Update Posted (Actual): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Bacterial Infections and Mycoses; Lymphadenopathy; Lymphoma; Leukemia; Hodgkin Disease; Recurrence; Lymphoma, Non-Hodgkin; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Mycosis Fungoides; Sezary Syndrome; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell; Immunoblastic Lymphadenopathy; Leukemia, Large Granular Lymphocytic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Micronutrients; Vitamins; Antioxidants; Vitamin B Complex; Bendamustine Hydrochloride; Thioctic Acid
• Other Study ID Numbers: IRB00028206; P30CA012197 (U.S. NIH Grant/Contract); NCI-2014-01281 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CCCWFU 28314 (Other Identifier: Comprehensive Cancer Center of Wake Forest University)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No