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

NCT ID: NCT00963274

Last Updated: 2018-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-04-26
• Study Completion Date: 2018-04-13

Brief 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). Bortezomib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

bortezomib + romidepsin

Bortezomib 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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Starting dose: 1.3 mg/sq m

Romidepsin

Intervention Type: DRUG

Starting dose: 8 mg/sq m

Interventions

Bortezomib

Starting dose: 1.3 mg/sq m

Intervention Type: DRUG

Romidepsin

Starting dose: 8 mg/sq m

Intervention Type: DRUG

Other Intervention Names

Velcade; PS-341; depsipeptide; FK288

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Beata Holkova, MD

Role: PRINCIPAL_INVESTIGATOR

Massey Cancer Center

Thomas C. Shea, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Steven Grant, MD

Role: STUDY_CHAIR

Virginia Commonwealth University

Sho Ma, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University & Robert H Lurie Comprehensive Cancer Center

Amy Kimball, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland Greenebaum Cancer Center

Nishitha Reddy, MBBS

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center, Vanderbilt University

Locations

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Vanderbilt-Ingram Cancer Center, Vanderbilt University

Nashville, Tennessee, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28103725 (View on PubMed)

Related Links

http://www.massey.vcu.edu/

VCU Massey Cancer Center

Other Identifiers

P30CA016059

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCC-12215

Identifier Type: OTHER

Identifier Source: secondary_id

R21CA137823

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000652509

Identifier Type: REGISTRY

Identifier Source: secondary_id

MCC-12215

Identifier Type: -

Identifier Source: org_study_id