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B-cell Adult Acute Lymphoblastic LeukemiaPhase 1NCT02168907

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

A Phase 1 study testing 6,8-bis(benzylthio)octanoic acid, bendamustine hydrochloride and rituximab in people with B-cell Adult Acute Lymphoblastic Leukemia and B-cell Chronic Lymphocytic Leukemia, run by Wake Forest University Health Sciences at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
6,8-bis(benzylthio)octanoic acid, bendamustine hydrochloride and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Dec 2014to Feb 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Comprehensive Cancer Center of Wake Forest University

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
6,8-bis(benzylthio)octanoic acid, bendamustine hydrochloride, rituximab, laboratory biomarker analysis
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 6,8-bis(benzylthio)octanoic acidDrug

    Also called alpha-lipoic acid analogue CPI-613, CPI-613

    Given IV

  • bendamustine hydrochlorideDrug

    Also called bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Treanda

    Given IV

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02168907
Study groupRoleWhat they receive
Treatment (CPI-613, bendamustine hydrochloride, rituximab)ExperimentalPatients 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.
Receives: Drug: 6,8-bis(benzylthio)octanoic acid; Drug: bendamustine hydrochloride; Biological: rituximab; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 4 weeks

Secondary outcomes (6)

  1. Response rate assessed by the modified IWG criteria

    The response rate and its 95% confidence interval will be assessed.

    Measured: Up to 2 years

  2. Disease control rate assessed by the modified IWG criteria

    The DCR and its 95% confidence interval will be assessed.

    Measured: Up to 2 years

  3. Overall survival assessed by the modified IWG criteria

    OS curves will be plotted using Kaplan-Meier methods.

    Measured: Up to 2 years

  4. Progression free survival assessed by the modified IWG criteria

    PFS curves will be plotted using Kaplan-Meier methods and median PFS will be examined.

    Measured: Up to 2 years

  5. Bone marrow biopsy analysis

    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.

    Measured: Baseline

  6. Incidence of toxicities graded according to NCI CTCAE

    Will be examined by looking at each toxicity identified earlier in the protocol by grade.

    Measured: Up to 6 courses

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Why it stopped: Slow Accruals

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02168907
Sponsor's protocol ID
IRB00027759
Other IDs
NCI-2014-01280, CCCWFU 28114, P30CA012197
Status last verified
Jun 2018
First submitted
18 Jun 2014
Last updated
2 Jul 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 6,8-bis(benzylthio)octanoic acid, bendamustine hydrochloride and rituximab in people with B-cell Adult Acute Lymphoblastic Leukemia and B-cell Chronic Lymphocytic Leukemia, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Slow Accruals). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02168907.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2018.

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