Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

NCT00131937 | Completed Phase 2 Results

• 3 other identifiers: NCI-2014-00658E1404U10CA021115
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well sorafenib works in treating patients with recurrent diffuse large B-cell non-Hodgkin's lymphoma. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Conditions

Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response (OR) Rate

  Response was assessed using the criteria from International Workshop to Standardize Criteria for NHL (Cheson, 1999). OR=complete response(CR)+complete response/uncertain(CRu)+partial response(PR) CR: 1)Disappearance of clinical/radiographic evidence of disease (dz) and all dz-related B-symptoms; normalization of biochemical abnormalities attributed to NHL; 2)Lymph nodes and nodal masses regress to normal size; 3)Spleen, if enlarged before therapy, has decreased in size and is not palpable; 4)Complete resolution of lymphoma in bone marrow biopsy CRu: Meet criteria 1 and 3 above but with ≥1 of the followings. Residual dominant nodal mass \>1.5 cm in greatest diameter that has decreased by \>75%. Indeterminate bone marrow. PR: ≥50% decrease in SPD (sum of products of diameters) of 6 largest dominant nodes or nodal masses. No increase in size of liver or spleen. No unequivocal progression in nonmeasurable or nondominant sites. Splenic/hepatic nodules regress ≥50% in SPD. No new dz sites.

  Assessed at the end of Cycle 2 and Cycle 6 (1 cycle = 28 days). Then every 3 months beginning Cycle 9 if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years.

Secondary Outcomes (2)

• Progression-Free Survival (PFS)

  Assessed after month 2 and month 6, then every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years

• Overall Survival

  Assessed after month 2 and month 6, then every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years.

Study Arms (1)

Treatment (sorafenib tosylate)

EXPERIMENTAL

Patients receive oral sorafenib 400 mg PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: sorafenib tosylate

Interventions

sorafenib tosylate DRUG

Given orally

Also known as: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar, SFN

Treatment (sorafenib tosylate)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed recurrent de novo or transformed diffuse large B cell lymphoma (DLBCL) or one of its variants according to WHO classification (centroblastic, immunoblastic, T-cell/histiocyte rich and anaplastic variants)
• Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1
• Patients must have measurable disease as defined in section 6 assessed within 4 weeks of registration
• Patients must have failed one or more prior Non-Hodgkin lymphoma (NHL) chemotherapy or antibody therapy with curative intent; autologous stem cell transplant is permitted
• Leukocytes \>= 2,000/mm\^3
• Absolute neutrophil count \>= 1,000/mm\^3
• Platelets \>= 75,000/ mm\^3
• Total bilirubin =\< 2.0 X normal institutional limits
• Aspartate Aminotransferase (AST) =\< 2.5 X institutional upper limit of normal
• Alanine Aminotransferase (ALT) =\< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits; creatinine clearance calculated or measured at \>= 60 ml/min/1.73m\^2 if creatinine level is above institutional limits
• The prothrombin time (PT)/international normalized ratio (INR) within Institutional limits of normal
• Patients with underlying hypertension as defined by blood pressures averaging greater than 140/90 on two separate clinic visits are eligible if hypertension has been controlled by standard nonpharmacologic and pharmacologic therapy
• Patients must be physically able to orally ingest tablets

You may not qualify if:

• Central nervous system (CNS) involvement
• Previously treated with Sorafenib (BAY 43-9006) or other small molecule targeted inhibitors of mitogen-activated protein kinase (MAPK) signaling intermediates or angiogenesis (e.g. bevacizumab)
• Progressed within 60 days of last therapy
• Prior allogeneic stem cell transplant
• Candidates for potentially curative therapy, such as hematopoietic stem cell transplantation (HSCT)
• Currently receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
• Active HIV infection, because of possible pharmacokinetic interactions of anti-retroviral therapy with BAY43-9006
• Evidence of bleeding diathesis
• Currently taking the cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine and phenobarbital), rifampin or St. John's Wort
• Pregnant or Breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Eastern Cooperative Oncology Group

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell, Peripheral; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, T-Cell, Cutaneous

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The study did not meet pre-specified criteria for continuing to second stage accrual (at least one response among the first 12 eligible patients), and was therefore closed per protocol without full accrual.

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG Statistical Office

617-632-3012

Study Officials

• Sandra Horning

  Eastern Cooperative Oncology Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2005
• First Posted: August 19, 2005
• Study Start: October 1, 2005
• Primary Completion: September 1, 2011
• Study Completion: August 1, 2012
• Last Updated: September 3, 2015
• Results First Posted: September 3, 2015

Record last verified: 2015-07

Locations

US (1)