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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Pfizer
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01281917
First received: January 20, 2011
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Non-Hodgkins Lymphoma
Drug: Velcade
Drug: Temsirolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Velcade and Temsirolimus for Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Overall Response Rate and Progression Free Survival [ Time Frame: 60 months from start ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival [ Time Frame: 60 months from start ] [ Designated as safety issue: No ]
    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:
  • Safety of this regimen [ Time Frame: 36 months from start ] [ Designated as safety issue: Yes ]
    Safety of the regimen will be measured by frequency and severity of adverse events.

  • Complete Response Rate [ Time Frame: 60 months from start ] [ Designated as safety issue: No ]
    The complete response rate (CR) to therapy as defined by International Lymphoma Response Criteria.

  • Tolerability of the regimen [ Time Frame: 36 months from start ] [ Designated as safety issue: No ]
    Tolerability of the regimen is measured by the number of subjects able to complete the therapy as planned.

  • Duration of Response [ Time Frame: 60 months from start ] [ Designated as safety issue: No ]
    Duration of Response is how long a response to therapy is held before a subject has progressive disease.

  • Overall Survival [ Time Frame: 60 months from start ] [ Designated as safety issue: No ]
    Length of time from enrollment until death.


Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01281917

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
Bellin Memorial Hospital, Inc
Green Bay, Wisconsin, United States, 54313
Aurora Baycare Medical Center-GreenBay
Green Bay, Wisconsin, United States, 54143
St Vincent Regional Cancer Center CCOP
Green Bay, Wisconsin, United States, 54301
Gunderson Lutheran Health System
LaCrosse, Wisconsin, United States, 54601
University Of Wisconsin Cancer Center
Madison, Wisconsin, United States, 53792
UW Health Oncology- 1 S Park
Madison, Wisconsin, United States, 53715
Aurora BayCare Medical Center
Marinette, Wisconsin, United States
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Columbia St Mary's, Inc
Milwaukee, Wisconsin, United States, 53211
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
Investigators
Principal Investigator: Brad S Kahl, MD Universtity of Wisconsin- Madison
Study Chair: Timothy S Fenske, MD Medical College of Wisconsin
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01281917     History of Changes
Other Study ID Numbers: H-2010-0393, HO10407
Study First Received: January 20, 2011
Last Updated: May 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
velcade
temsirolimus
non-hodgkins lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Sirolimus
Everolimus
Bortezomib
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014