Combination CCI-779 (Temsirolimus) and Bortezomib (Velcade) in Relapsed and/or Relapsed/Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Collaborators:
Wyeth is now a wholly owned subsidiary of Pfizer
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Irene Ghobrial, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00483262
First received: June 5, 2007
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

The purpose of this research study is to determine the safety of CCI-779 (Temsirolimus) and bortezomib (Velcade), and the highest dose of this drug that can be given to people safely. We will also be looking at how the combination of the two drugs may work against multiple myeloma. CCI-779 (Temsirolimus) is a drug that appears to stop myeloma cells from growing.


Condition Intervention Phase
Multiple Myeloma
Drug: CCI-779
Drug: Bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Trial of Combination CCI-779 (Temsirolimus) and Bortezomib (Velcade) in Relapsed and/or Relapsed/Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Toxicity. Number of Patients With Specific Toxicities Are Reported. [ Time Frame: 10 months ] [ Designated as safety issue: Yes ]
    Toxicity of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with multiple myeloma.

  • Best Response to Combination Treatment [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Response rate of PR or better to the combination treatment of CCI-779 (Temsirolimus) and bortezomib (Velcade) in patients with relapsed or refractory multiple myeloma


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 10 months ] [ Designated as safety issue: No ]
    Median time to progression or death


Enrollment: 63
Study Start Date: May 2007
Study Completion Date: February 2012
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CCI779 and Bortezomib Phase I/II
In Phase I part, 15 or 25 mg temsirolimus (CCI-779)and 1·3 or 1·6 mg/m² bortezomib was given once a week.In Phase II, patients received intravenous temsirolimus once a week on days 1, 8, 15, 22, and 29 for a cycle of 35 days, and intravenous bortezomib once a week on days 1, 8, 15, and 22 for a cycle of 35 days, the MTD ascertained in the Phase I part.
Drug: CCI-779
Given by injection once a week for 5 weeks (5 weeks equals one cycle) for up to 8 cycles
Other Name: Temsirolimus
Drug: Bortezomib
Given by injection once a week for 4 weeks (a cycle equals 5 weeks) for up to 8 cycles
Other Name: Velcade

Detailed Description:
  • Since we are looking for the highest dose of CCI-779 (Temsirolimus) given in combination with bortezomib (Velcade) that can be given to people without causing the most serious or unmanageable side effects, not everyone who participates in this study will be receiving the same amount of either drug.
  • During the study treatment, participants will be given some medications to decrease the chance they they will have an allergic reaction to CCI-779 (Temsirolimus). After these drugs are given, participants will be receive bortezomib (Velcade) by injection followed by an injection of CCI-779 (Temsirolimus). These drugs wil be given once a week for four weeks (on Days 1, 8, 15, and 22). On the fifth week (Day 29), participants will be given only CCI-779 along with the drugs to decrease the chance of an allergic reaction.
  • The cycle will last 35 days and will occur twice before the doctor evaluates for response. The cycles will be repeated for up to 8 cycles as long as the participant does not have any severe or unmanageable side effects and the disease is responding to treatment.
  • While receiving study treatment, participants will be seen at the clinic at the start of each cycle for the following: complete physical examination, blood work, urine collection, x-ray of bones (if study doctor deems necessary) and an electrocardiogram (prior to treatment and at the end of treatment)
  • A bone skeletal survey will be performed at the end of treatment to measure the size of the participants tumors.
  • After 8 cycles of treatment or if the participant has ended treatment, more tests will be performed. A physical exam, blood work, urine collection, skeletal survey, electrocardiogram, bone marrow biopsy and aspirate will be performed.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • Must have received prior therapy for their myeloma and have relapsed and/or relapsed/refractory multiple myeloma
  • Monoclonal protein in the serum of greater than or equal to 1 gm/dL or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200mg/24 hours, or measurable light chains by free light chain assay of greater than or equal to 10mg/dl, or measurable plasmacytoma
  • ECOG Performance Status 0, 1 or 2
  • Laboratory values as outlined in the protocol

Exclusion Criteria:

  • Uncontrolled infection
  • Cytotoxic chemotherapy less than 2 weeks, or biologic therapy less than 2 weeks, or corticosteroids less than 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma.
  • Pregnant or nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational within 14 days before enrollment
  • Known to be HIV positive
  • Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Hypersensitivity to bortezomib, boron or mannitol
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical trial
  • Patients who may need or are receiving live vaccines for immunization
  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: NCT00483262

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University in Saint Louis
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Dana-Farber Cancer Institute
Wyeth is now a wholly owned subsidiary of Pfizer
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Irene Ghobrial, MD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00483262     History of Changes
Other Study ID Numbers: 06-365
Study First Received: June 5, 2007
Results First Received: June 27, 2011
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Temsirolimus
Bortezomib

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014