Study of Velcade and Temsirolimus for Relapsed or Refractory Non-Hodgkin Lymphoma

• ClinicalTrials.gov Identifier: NCT01281917
• Recruitment Status: Completed
• First Posted: January 24, 2011
• Results First Posted: August 21, 2017
• Last Update Posted: August 21, 2017
• Sponsor: University of Wisconsin, Madison
• Collaborators: Millennium Pharmaceuticals, Inc.; Pfizer; National Cancer Institute (NCI)
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

Brief Summary:

The investigators want to find out if the drugs Velcade and temsirolimus given together are effective in treating cancer. Velcade and temsirolimus are each FDA approved individually for certain types of cancer (Velcade for multiple myeloma and mantle cell lymphoma, and temsirolimus for renal cell carcinoma) but are not currently approved in combination for B-cell non-Hodgkin lymphoma. The investigators are trying to find out if giving these 2 drugs together will improve the period of time that the patient's cancer is stopped or slowed from growing and causing symptoms.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkins Lymphoma	Drug: Velcade; Drug: Temsirolimus	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Velcade and Temsirolimus for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
• Study Start Date: February 2011
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Velcade plus Temsirolimus; Velcade 1.6 mg/m2 weekly (days 1, 8, 15, and 22) Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29) Treat for up to 6 cycles, cycles are 35 days long.	Drug: Velcade; Velcade, 1.6 mg/m2 weekly (days 1, 8, 15, and 22); Other Name: bortezomib, PS-341; Drug: Temsirolimus; Temsirolimus 25mg IV weekly (days 1, 8, 15, 22, and 29); Other Name: Torisel

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate [ Time Frame: Up to 60 months ]
   The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by overall response rate (ORR) to therapy. ORR is the sum of patients with a Complete Response and Partial Response to therapy. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete REsponse (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
2. Progression Free Survival [ Time Frame: Up to 60 months ]
   The primary objective of this study is to determine whether Velcade in combination with temsirolimus provides benefit to subjects with relapsed or refractory B-cell non-Hodgkin lymphoma as assessed by progression-free survival (PFS).

Secondary Outcome Measures :

1. Safety of This Regimen [ Time Frame: Up to 36 months ]
   Safety of the regimen will be measured by frequency and severity of adverse events.
2. Complete Response Rate [ Time Frame: Up to 60 months ]
   The complete response rate (CR) to therapy as defined by International Lymphoma Response Criteria.
3. Tolerability of the Regimen [ Time Frame: Up to 36 months ]
   Tolerability of the regimen is measured by the number of subjects able to complete the therapy as planned.
4. Duration of Response [ Time Frame: Up to 60 months ]
   Duration of Response is how long a response to therapy is held before a subject has progressive disease.
5. Overall Survival [ Time Frame: Up to 60 months ]
   Length of time from enrollment until death.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Relapsed or refractory B-cell non-Hodgkin lymphoma which includes: diffuse large B-cell lymphoma; primary mediastinal large B-cell lymphoma; follicular lymphoma (grade 1, 2 or 3); mantle cell lymphoma; small lymphocytic lymphoma; marginal zone lymphoma; lymphoplasmacytic lymphoma; B-cell lymphoblastic lymphoma; or Burkitt lymphoma. "Grey-zone" lymphomas must be approved by the Wisconsin Oncology Network (WON) Study Chair or Principal Investigator prior to enrollment.
• At least one measurable tumor mass (>1.5 cm in the long axis and > 1.0 cm in the short axis) that has not been previously irradiated, or has grown since previous irradiation.
• Documented relapse or progression following prior antineoplastic therapy.
• No clinical or documented radiographic evidence of central nervous system lymphoma.
• Eastern Cooperative Oncology Group [ECOG] performance status of 0-2.
• The following clinical laboratory values within 14 days prior to enrollment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 cells / L
• Platelets ≥ 100 x 109 cells / L
• Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤ 3X the upper limit of normal (ULN)
• Total bilirubin ≤ 2X the upper limit of normal (ULN).
• Calculated creatinine clearance ≥40 mL/min (using the Cockcroft-Gault equation).
• Female subjects must be either post-menopausal for at least 1 year or surgically sterilized, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of Velcade, or agree to completely abstain from heterosexual intercourse.
• Male subjects, even if surgically sterilized (ie, status postvasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.

Exclusions:

• Antineoplastic, experimental, or radiation therapy within 14 days prior to enrollment, or 21 days prior to Day 1 of Cycle 1.
• Radioimmunoconjugates within 10 weeks of Day 1 of Cycle 1.
• Autologous stem cell transplant within 3 months before Day 1 of Cycle 1, or any prior history of allogeneic stem cell transplant.
• Platelet transfusion within 7 days of Day 1 of Cycle 1.
• Ongoing therapy with glucocorticoids. Prednisone ≤15 mg per day or its equivalent is allowed.
• Patient has Grade 2 or greater peripheral neuropathy within 14 days before enrollment.
• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Patient has hypersensitivity to Velcade, boron or mannitol.
• Female subjects that are pregnant or breast-feeding.
• Serious medical or psychiatric illness that is likely to interfere with participation
• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
• Prior therapy with both Velcade and temsirolimus. Patients who have previously been treated with either Velcade or temsirolimus (but not both) are eligible.
• Radiation therapy within 3 weeks before randomization.
• Patients must not be taking the following strong CyP3A inducers at study entry: phenytoin, phenobarbital, rifampin, carbamazepin, rifabutin, rifampicin, a one week washout period is required.

Contacts and Locations

Locations

United States, South Dakota

Rapid City Regional Hospital John T. Vucurevich Cancer Care Institute

Rapid City, South Dakota, United States, 57701

United States, Wisconsin

Aurora Baycare Medical Center-GreenBay

Green Bay, Wisconsin, United States, 54143

St Vincent Regional Cancer Center CCOP

Green Bay, Wisconsin, United States, 54301

Bellin Memorial Hospital, Inc

Green Bay, Wisconsin, United States, 54313

Gunderson Lutheran Health System

La Crosse, Wisconsin, United States, 54601

UW Health Oncology- 1 S Park

Madison, Wisconsin, United States, 53715

University Of Wisconsin Cancer Center

Madison, Wisconsin, United States, 53792

Aurora BayCare Medical Center

Marinette, Wisconsin, United States

Marshfield Clinic

Marshfield, Wisconsin, United States, 54449

Columbia St Mary's, Inc

Milwaukee, Wisconsin, United States, 53211

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Aurora Sheboygan Memorial Medical Center

Sheboygan, Wisconsin, United States, 53081

Aurora Medical Center in Summit

Summit, Wisconsin, United States, 53066

Aurora Medical Center in Two Rivers

Two Rivers, Wisconsin, United States, 54241

Waukesha Memorial Hospital

Waukesha, Wisconsin, United States, 53188

Aspirus Wausau Hospital

Wausau, Wisconsin, United States, 54401

Aurora Health Care Metro, Inc.

Wauwatosa, Wisconsin, United States, 53226

UW Cancer Center-Riverview

Wisconsin Rapids, Wisconsin, United States, 54494

Sponsors and Collaborators

University of Wisconsin, Madison

Millennium Pharmaceuticals, Inc.

Pfizer

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Brad S Kahl, MD; Universtity of Wisconsin- Madison
• Study Chair: Timothy S Fenske, MD; Medical College of Wisconsin

More Information

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT01281917 History of Changes
• Other Study ID Numbers: HO10407; H-2010-0393 ( Other Identifier: IRB )
• First Posted: January 24, 2011
• Results First Posted: August 21, 2017
• Last Update Posted: August 21, 2017
• Last Verified: July 2017

Keywords provided by University of Wisconsin, Madison:

velcade; temsirolimus; non-hodgkins lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Sirolimus; Bortezomib; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents