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

NCT02168907 | Terminated Phase 1 FDA Drug

• 4 other identifiers: IRB00027759NCI-2014-01280CCCWFU 28114P30CA012197
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

B-cell Adult Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; 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 Grade III Lymphomatoid Granulomatosis; 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; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• 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)

  Will be accomplished by monitoring toxicities and using the dose escalation plan.

  4 weeks

Secondary Outcomes (6)

• Response rate assessed by the modified IWG criteria

  Up to 2 years

• Disease control rate assessed by the modified IWG criteria

  Up to 2 years

• Overall survival assessed by the modified IWG criteria

  Up to 2 years

• Progression free survival assessed by the modified IWG criteria

  Up to 2 years

• Bone marrow biopsy analysis

  Baseline

Study Arms (1)

Treatment (CPI-613, bendamustine hydrochloride, rituximab)

EXPERIMENTAL

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.

Drug: 6,8-bis(benzylthio)octanoic acid; Drug: bendamustine hydrochloride; Biological: rituximab; Other: laboratory biomarker analysis

Interventions

6,8-bis(benzylthio)octanoic acid DRUG

Given IV

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

Treatment (CPI-613, bendamustine hydrochloride, rituximab)

bendamustine hydrochloride DRUG

Given IV

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

Treatment (CPI-613, bendamustine hydrochloride, rituximab)

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (CPI-613, bendamustine hydrochloride, rituximab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (CPI-613, bendamustine hydrochloride, rituximab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Intraocular Lymphoma; Lymphoma, B-Cell, Marginal Zone; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Mycosis Fungoides; Sezary Syndrome; Leukemia, Hairy Cell; Waldenstrom Macroglobulinemia

Interventions

devimistat; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Eye Neoplasms; Neoplasms by Site; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zanetta Lamar

  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: December 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: July 2, 2018

Record last verified: 2018-06

Locations

US (1)