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LeukemiaPhase 1NCT00963274

Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

A Phase 1 study testing Bortezomib and Romidepsin in people with Leukemia and Lymphoma, run by Virginia Commonwealth University at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and best dose of giving bortezomib and romidepsin together in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), indolent B-cell lymphoma, peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Lymphoma
What is being tested?
Bortezomib and Romidepsin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
5 sitesUnited States
Study dates
26 Apr 2010to 13 Apr 2018
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

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:
  • CLL or SLL, relapsed or refractory
  • Indolent B-cell lymphoma, relapsed or refractory:
  • Follicle center lymphoma, follicular or diffuse
  • Marginal zone B-cell lymphoma (splenic, nodal, extranodal [this includes mucosa associated lymphoid tissue (MALT)])
  • Lymphoplasmacytic lymphoma
  • PTCL, relapsed or refractory:
  • Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK)-positive
  • Anaplastic large cell lymphoma, ALK-negative
  • Angioimmunoblastic T-cell lymphoma
  • Enteropathy-associated T-cell lymphoma
  • Extranodal natural killer (NK)/T-cell lymphoma, nasal type
  • Hepatosplenic T-cell lymphoma
  • PTCL, not otherwise specified (NOS)
  • Subcutaneous panniculitis-like T-cell lymphoma
  • CTCL:
  • CTCL with subtypes of mycosis fungoides Stage IB or higher, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma who have failed a previous systemic treatment, as per the following:
  • Stage IA plaque, IB, or IIA: At least 4 prior conventional and/or experimental regimens (topical or systemic, including psoralen-ultraviolet light [PUVA] and systemic corticosteroids)
  • Stage IIB, III, or IV: At least 1 prior systemic regimen (systemic corticosteroids alone or PUVA alone do not count as systemic regimens for this purpose) NOTE: Repeated use of the same regimen is considered 1 regimen
  • Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
  • >= 6 months have elapsed since allogeneic transplant
  • No Graft vs. Host Disease (GVHD) is present
  • Not currently on immunosuppressive therapy
  • No prior or concurrent CNS malignancy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • ANC > 1,500/mm^3
  • Platelet count > 75,000/mm^3
  • Hemoglobin > 7.5 g/dL (transfusion allowed)
  • Serum creatinine ≤ 1.2 mg/dL or actual or calculated creatinine clearance > 60 mL/min
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN)
  • Bilirubin ≤ ULN
  • Serum potassium ≥ 3.5 mEq/L (supplementation allowed)
  • Serum magnesium ≥ 1.7 mEq/L (supplementation allowed)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception
  • Willing and able to comply with protocol requirements
  • No prior severe allergic reactions to bortezomib, boron, mannitol, or romidepsin
  • No progressing toxicity secondary to bortezomib
  • No grade 1 peripheral neuropathy with pain or ≥ grade 2 peripheral neuropathy by NCI-CTCAE criteria (v4.0) within the past 14 days
  • No condition related to ischemic heart disease, heart failure, or the risk of torsades de pointes or sudden cardiac death, including any of the following:
  • History of sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implantable cardiac defibrillator
  • Baseline heart rate > 140 beats per minute
  • Known congenital long QT syndrome
  • QTc interval > 480 milliseconds
  • Type II second-degree atrio-ventricular (AV) block, third-degree AV block, or ventricular rate < 50 beats per minute
  • Myocardial infarction within the past 6 months
  • Patients who have had a myocardial infarction 6-12 months ago are eligible provided they are asymptomatic and have a negative cardiac risk assessment (i.e., treadmill stress test, nuclear medicine stress test, or stress echocardiogram)
  • Angina upon ordinary physical activity
  • Angina only with strenuous, rapid, or prolonged exertion allowed
  • ECG with evidence of cardiac ischemia, as defined by the following:
  • ST depression of ≥ 2 mm, measured from isoelectric line to ST segment
  • T-wave inversion ≥ 4 mm, measured from isoelectric line to peak of T-wave
  • NYHA class II-IV congestive heart failure
  • Known left ventricular ejection fraction < 40% by MUGA scan or < 50% by echocardiogram or MRI
  • Known hypertrophic cardiomegaly or restrictive cardiomyopathy
  • No uncontrolled hypertension, defined as persistent blood pressure ≥ 160/95 mm Hg despite medical management
  • No clinically significant active infection, including known HIV infection or hepatitis B or C
  • No other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ malignancy, or curatively treated low-risk prostate cancer
  • No concurrent medical condition that, in the investigator's opinion, would compromise study treatment or assessment of toxicity

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 3 weeks since prior chemotherapy, radiation therapy or investigational agents. If steroids for cancer control have been used, patients must be off theses agents for at least 1 week before starting treatment. (Maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose less than 10 mg/day is permitted)
  • Prior allogeneic stem cell transplantation allowed provided all of the following conditions are met:
  • Greater than or equal to 6 months have elapsed since allogeneic transplant
  • No Graft vs. Host Disease (GVHD) is present
  • More than 4 weeks since prior bortezomib
  • No concurrent oral hormonal contraceptives
  • No concurrent potent or moderate CYP3A4 inhibitors
  • No concurrent anti-arrhythmic agents
  • No concurrent treatment with any drugs that are generally accepted to having a risk of causing torsades de pointes (class 1 drugs)
  • Class 2 or 3 drugs allowed at the discretion of the investigator
  • No other concurrent systemic therapy for the malignancy
  • Concurrent warfarin (coumadin) allowed

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • University of Maryland Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Robert H. Lurie Comprehensive Cancer Center, Northwestern University

    Chicago, Illinois, 60611

  • Vanderbilt-Ingram Cancer Center, Vanderbilt University

    Nashville, Tennessee, 37232

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

Other trials in United States

About this study

Official title: Phase I Study of Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Indolent B-Cell Lymphoma, Peripheral T-Cell Lymphoma or Cutaneous T-Cell Lymphoma

This phase I trial studies the side effects and best dose of giving bortezomib and romidepsin together in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), indolent B-cell lymphoma, peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Bortezomib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) for the combination of bortezomib and romidepsin administered weekly x 3 every (q) 4wk in patients with CLL/SLL, indolent B-cell lymphoma, PTCL or cutaneous T-cell lymphoma (CTCL).

Secondary

  • Determine safety and tolerance and describe the toxicities of the combination.
  • Demonstrate adequate methods for the assessment of pharmacodynamic responses of CLL cells to the combination with respect to effects on NF-kappa B (nuclear RelA and processing of p52 as a marker of p100 processing), expression of the NF-kappa B-dependent proteins XIAP and Bcl-xL, and Bim, and document pharmacodynamic responses observed in the course of this study * Document the pharmacodynamic responses associated with this regimen in these patients.
  • Document the anticancer activity of this regimen in these patients.

OUTLINE: Patients receive bortezomib IV over 3-5 seconds and romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Blood samples from patients with chronic lymphocytic leukemia are collected at baseline and after day 1 of course 1 of study treatment for pharmacodynamic and correlative laboratory studies.

Conditions
Leukemia, Lymphoma
Being tested
Bortezomib, Romidepsin
Keywords
refractory chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent small lymphocytic lymphoma, contiguous stage II small lymphocytic lymphoma, noncontiguous stage II small lymphocytic lymphoma, stage I small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, hepatosplenic T-cell lymphoma, nodal marginal zone B-cell lymphoma, peripheral T-cell lymphoma
Medical subject headings
Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Extranodal NK-T-Cell, Lymphoma, Large-Cell, Anaplastic, Immunoblastic Lymphadenopathy, Lymphoma, B-Cell, Marginal Zone, Lymphoma, T-Cell, Peripheral

What participants receive

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

  • BortezomibDrug

    Also called Velcade, PS-341

    Starting dose: 1.3 mg/sq m

  • RomidepsinDrug

    Also called depsipeptide, FK288

    Starting dose: 8 mg/sq m

Study groups in NCT00963274
Study groupRoleWhat they receive
bortezomib + romidepsinExperimentalBortezomib via a short intravenous infusion (3-5 seconds) followed by romidepsin via a 4 hour intravenous infusion weekly x 3 every 4 weeks. In order to identify appropriate doses, different subjects will be treated with different drug doses and observed for the effects, especially the side effects associated with higher doses.
Receives: Drug: Bortezomib; Drug: Romidepsin

What is being measured

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

  1. Maximum tolerated dose

    Dose at which no more than 1 dose-limiting toxicity is observed in as many as 6 patients

    Measured: 2 years

Secondary outcomes (1)
  1. Pharmacodynamic responses

    To explore candidate pharmacodynamic markers for use in subsequent phase II trials.

    Measured: 2 years

Timeline

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

  1. First posted21 Aug 2009 (estimated)
  2. Study start26 Apr 2010
  3. Primary completion17 Jul 2014
  4. Study completion13 Apr 2018

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00963274
Sponsor's protocol ID
MCC-12215
Other IDs
P30CA016059, MCC-12215, R21CA137823, CDR0000652509
Status last verified
Apr 2018
First submitted
20 Aug 2009
Last updated
23 Apr 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Holkova B, Yazbeck V, Kmieciak M, Bose P, Ma S, Kimball A, Tombes MB, Shrader E, Wan W, Weir-Wiggins C, Singh A, Hogan KT, Conine S, Sankala H, Roberts JD, Shea TC, Grant S. A phase 1 study of bortezomib and romidepsin in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, indolent B-cell lymphoma, peripheral T-cell lymphoma, or cutaneous T-cell lymphoma. Leuk Lymphoma. 2017 Jun;58(6):1349-1357. doi: 10.1080/10428194.2016.1276287. Epub 2017 Jan 19.

    PubMed 28103725

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bortezomib and Romidepsin in people with Leukemia and Lymphoma, run by Virginia Commonwealth University at 5 sites 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?

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: finished, as of the sponsor's last update on 23 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose (time frame: 2 years). 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 NCT00963274, which also lists 1 linked publication.

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 23 Apr 2018.

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Clinical Trial NCT00963274 | AzTrials