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

NCT02168140 | Completed Phase 1 FDA Drug

• 4 other identifiers: IRB00028206NCI-2014-01281CCCWFU 28314P30CA012197
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral 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 Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

Other Outcomes (5)

• RR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma

  Up to 3 years

• DCR, derived from the modified IWG criteria and the International Cutaneous Lymphoma (Olsen criteria) for cutaneous lymphoma

  Up to 3 years

• OS

  Time from first dose of 6,8-bis(benzylthio)octanoic acid to death by any cause, assessed up to 3 years

Study Arms (1)

Treatment (CPI-613 and bendamustine hydrochloride)

EXPERIMENTAL

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

Interventions

6,8-bis(benzylthio)octanoic acid DRUG

Given IV

Also known as: alpha-lipoic acid analogue CPI-613, CPI-613

Treatment (CPI-613 and bendamustine hydrochloride)

bendamustine hydrochloride DRUG

Given IV

Also known as: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda

Treatment (CPI-613 and bendamustine hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell, Peripheral; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Leukemia, Large Granular Lymphocytic

Interventions

devimistat; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphadenopathy; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rakhee Vaidya

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 20, 2014
• Study Start: September 1, 2014
• Primary Completion: April 18, 2019
• Study Completion: September 15, 2022
• Last Updated: February 13, 2024

Record last verified: 2023-12

Locations

US (2)