Ph II CHOP+Velcade in Mediastinal LBCL

This study has been terminated.
(Closed due to slow accrual)
Sponsor:
Collaborators:
Brigham and Women's Hospital
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Ann S. LaCasce, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00361621
First received: August 7, 2006
Last updated: November 30, 2012
Last verified: October 2009
  Purpose

The main purpose of this study is to begin to collect information and try to learn whether or not VELCADE, when added to standard chemotherapy with CHOP/Rituxan, works in treating patients mediastinal large B-cell lymphoma. Recent research has shown that this type of lymphoma shares features with Hodgkin's lymphoma, including the importance of a particular pathway in the tumor cells called the NF-kB pathway. VELCADE works in part by blocking this pathway.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: bortezomib
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Radiation: Radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of CHOP/Rituxan Plus VELCADE in Mediastinal Large B-cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To evaluate the rate of complete response to therapy defined as resolution of PET avidity in all previously documented sites at the completion of chemotherapy. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess toxicity [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • evaluate event-free survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • evaluate overall survival at 2 years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • assess early PET restaging after 3 cycles of chemotherapy. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: July 2006
Study Completion Date: May 2008
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: bortezomib
    Given intravenously on day 1 and day 4 of a 21-day cycle for 6 cycles
    Other Name: Velcade
    Drug: Rituximab
    Given intravenously on day 1 of a 21-day cycle for 6 cycles
    Drug: Cyclophosphamide
    Given intravenously on day 1 of a 21-day cycle for 6 cycles
    Drug: Doxorubicin
    Given intravenously on day 1 of a 21-day cycle for 6 cycles
    Drug: Vincristine
    Given intravenously on day 1 of a 21-day cycle for 6 cycles
    Drug: Prednisone
    Taken orally on days 2, 3, 4 and 5 or a 21-day cycle for 6 cycles
    Radiation: Radiation therapy
    After 6 cycles of chemotherapy there will be 3 weeks of radiation therapy
Detailed Description:
  • This is a single arm phase 2 study of CHOP/Rituxan plus VELCADE followed by involved field radiotherapy designed to evaluate the complete response to chemotherapy as determined by PET scan following six cycles of therapy. One cycle equals 21 days.
  • For each cycle, on Day 1, the patient will receive VELCADE intravenously, followed by rituxan, and then followed by CHOP chemotherapy. Before receiving these drugs, the patient will be given standard medications (Tylenol, Benadryl) to help minimize side effects. They will also continue to take prednisone by mouth on days 2, 3, 4, and 5. On Day 4, the patient will receive another dose of VELCADE.
  • Before the beginning of every cycle of study treatment, the following will be performed: Medical history; physical examination; and routine blood tests. After the 3rd and 6th cycle of study treatment, the patient will have tests to monitor the status of their disease. These include PET scan, CT scans, and standard blood tests.
  • After 6 cycles of chemotherapy, approximately 3 weeks of radiation therapy will begin. One month after completing radiation therapy, the patient will return to the clinic for a physical exam and blood tests. One month later, the following evaluations will occur: PET and CT scans; medical history; physical exam; routine blood tests.
  • There will be follow-up visits every 3 months for two years after the study treatment is completed.
  Eligibility

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

Inclusion Criteria:

  • Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.
  • Histologic Documentation: Histologically confirmed Primary Mediastinal Large B-cell Lymphoma with confirmatory immunoperoxidase stains including TRAF-1, and nuclear c-rel. All cases must be reviewed at Brigham and Women's Hospital.
  • Previously untreated patients with the exception of limited radiotherapy or steroids for SVC syndrome
  • Age > 18 years of age
  • Measurable Disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan.

Exclusion Criteria:

  • Patient has a platelet count of < 100,000/uL within 14 days before enrollment.
  • Patient has an absolute neutrophil count of < 1500/uL within 14 days before enrollment.
  • Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14 days before enrollment.
  • Patient has ³Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has New York Hospital 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. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum b-human chorionic gonadotropin (b-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs with 14 days before enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patient has a cardiac ejection fraction < 50% by echocardiogram or MUGA scan
  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: NCT00361621

Locations
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Ann LaCasce, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Ann S. LaCasce, MD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00361621     History of Changes
Other Study ID Numbers: 06-012, X05194
Study First Received: August 7, 2006
Last Updated: November 30, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
VELCADE

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014