A Phase 1 interventional study of 6,8-bis(benzylthio)octanoic acid and bendamustine hydrochloride in Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma and Adult Mixed Cellularity Hodgkin Lymphoma, sponsored by Wake Forest University Health Sciences. Completed at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-13.
Sponsored by Wake Forest University Health Sciences · Phase 1, Interventional, and Treatment
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.
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.
Exclusion Criteria:
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: 6,8-bis(benzylthio)octanoic acid · Drug: bendamustine hydrochloride
Given IV
Also known as: alpha-lipoic acid analogue CPI-613, CPI-613
Given IV
Also known as: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda
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.
Time frame: Up to 28 days
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.
Time frame: 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.
Time frame: 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 frame: 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 frame: 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.
Time frame: After course 6 (168 days)
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Wake Forest University Health Sciences