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

NCT00963274 | Completed Phase 1 DMC

• 4 other identifiers: MCC-12215P30CA016059R21CA137823CDR0000652509
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

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.

Conditions

Leukemia; Lymphoma

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

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

  2 years

Secondary Outcomes (1)

• Pharmacodynamic responses

  2 years

Study Arms (1)

bortezomib + romidepsin

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Romidepsin

Interventions

Bortezomib DRUG

Starting dose: 1.3 mg/sq m

Also known as: Velcade, PS-341

bortezomib + romidepsin

Romidepsin DRUG

Starting dose: 8 mg/sq m

Also known as: depsipeptide, FK288

bortezomib + romidepsin

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt-Ingram Cancer Center, Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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.

  PMID: 28103725 RESULT

Related Links

• VCU Massey Cancer Center

MeSH Terms

Conditions

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

Interventions

Bortezomib; romidepsin; Depsipeptides

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphadenopathy; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Beata Holkova, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

• Thomas C. Shea, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Steven Grant, MD

  Virginia Commonwealth University

  STUDY CHAIR

• Sho Ma, MD, PhD

  Northwestern University & Robert H Lurie Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Amy Kimball, MD, PhD

  University of Maryland Greenebaum Cancer Center

  PRINCIPAL INVESTIGATOR

• Nishitha Reddy, MBBS

  Vanderbilt-Ingram Cancer Center, Vanderbilt University

  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: August 20, 2009
• First Posted: August 21, 2009
• Study Start: April 26, 2010
• Primary Completion: July 17, 2014
• Study Completion: April 13, 2018
• Last Updated: April 23, 2018

Record last verified: 2018-04

Locations

US (5)