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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA016059 | U.S. NIH Grant/Contract | View source | |
| MCC-12215 | Other Identifier | VCU Massey Cancer Center | |
| R21CA137823 | U.S. NIH Grant/Contract | View source | |
| CDR0000652509 | Registry Identifier | PDQ |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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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.
OBJECTIVES:
Primary
Secondary
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bortezomib | Drug | Starting dose: 1.3 mg/sq m |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose | Dose at which no more than 1 dose-limiting toxicity is observed in as many as 6 patients | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamic responses | To explore candidate pharmacodynamic markers for use in subsequent phase II trials. | 2 years |
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DISEASE CHARACTERISTICS:
* Diagnosis of 1 of the following:
CLL or SLL, relapsed or refractory
Indolent B-cell lymphoma, relapsed or refractory:
PTCL, relapsed or refractory:
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:
Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:
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
Angina upon ordinary physical activity
ECG with evidence of cardiac ischemia, as defined by the following:
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)
No other concurrent systemic therapy for the malignancy
Concurrent warfarin (coumadin) allowed
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Robert H. Lurie Comprehensive Cancer Center, Northwestern University | Chicago | Illinois | 60611 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28103725 | Result | 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. |
| Label | URL |
|---|---|
| VCU Massey Cancer Center | View source |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| D017728 | Lymphoma, Large-Cell, Anaplastic |
| D007119 | Immunoblastic Lymphadenopathy |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000069286 | Bortezomib |
| C087123 | romidepsin |
| D047630 | Depsipeptides |
| ID | Term |
|---|---|
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
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| Romidepsin | Drug | Starting dose: 8 mg/sq m |
|
|
| University of Maryland Greenebaum Cancer Center |
| Baltimore |
| Maryland |
| 21201 |
| United States |
| University of North Carolina | Chapel Hill | North Carolina | 27599 | United States |
| Vanderbilt-Ingram Cancer Center, Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D000072281 | Lymphadenopathy |
| D016393 | Lymphoma, B-Cell |
| D001896 |
| Boron Compounds |
| D009930 | Organic Chemicals |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |