Bortezomib (Velcade) With Standard Chemotherapy for Relapsed or Refractory Follicular Lymphoma

This study has been terminated.
(Low accrual.)
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00510887
First received: August 1, 2007
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate the effectiveness and safety of combining bortezomib (Velcade) with rituximab, fludarabine, mitoxantrone, and dexamethasone in treating patients with follicular cell lymphoma.


Condition Intervention Phase
Lymphoma, Follicular
Drug: Bortezomib
Drug: Rituximab
Drug: Fludarabine
Drug: Mitoxantrone
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Bortezomib in Combination With Rituximab, Fludarabine, Mitoxantrone, and Dexamethasone (VR-FND) for Relapsed or Refractory Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Complete and Partial Response [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    • Complete Response: Complete disappearance of all detectable clinical and radiographic evidence of disease, disappearance of all disease-related symptoms and normalization of biochemical abnormalities (eg. LDH) definitely assignable to follicular lymphoma.
    • Partial Response requires the following:

      • greater than or equal to 50% decrease in the SPD of the 6 largest dominant nodes of nodal masses.
      • No increase in size of other nodes, liver, or spleen.
      • Splenic and hepatic nodes must regress by at least 50% in sum of the products (SPD).
      • Bone marrow assessment in irrelevant for determination of Partial Response since it is not measurable disease; however, if positive the type of cell should be reported.
      • No new lesions.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Duration of response is measured from time of treatment to time of disease progression

  • Percentage of Subjects Experiencing Progression Free Survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Progression free survival is measured from treatment to progression or death, whichever comes first. Progressive disease is measured as: 50% or greater increase from nadir in the sum of the products (SPD) of any previously identified abnormal node and the appearance of any new lesions during or at the end of treatment.

  • Percentage of Subjects Experiencing Overall Survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    Overall survival is from the day of enrollment to date of death from any cause.

  • Number of Participants With a Grade 3-4 Hematologic Toxicity. [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).

  • Number of Participants With Neuropathy, Any Grade [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria (CTC).


Enrollment: 14
Study Start Date: January 2007
Study Completion Date: September 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VR-FND

Bortezomib (VELCADER) 1.6 mg/m2 IV days 1 and 8 Rituximab 375 mg/m2 IV on day 1 Fludarabine 25 mg/m2 IV on days 1,2,3 Mitoxantrone 10 mg/m2 IV on day 2 Dexamethasone 20 mg orally on days 1,2,3,4,5 On day 1 the sequence of drug administration will be Bortezomib followed by Fludarabine followed by Rituximab.

Each cycle will be repeated every 28 days for 8 cycles maximum.

Drug: Bortezomib
Bortezomib 1.6 mg/m2 on days 1 and 8 of each 28-day cycle
Other Name: Velcade
Drug: Rituximab
Rituximab 375 mg/m2 IV on day 1
Drug: Fludarabine
Fludarabine 25 mg/m2 IV on days 1,2,3
Drug: Mitoxantrone
Mitoxantrone 10 mg/m2 IV on day 2
Other Name: Novantrone
Drug: Dexamethasone
Dexamethasone 20 mg orally on days 1,2,3,4,5

Detailed Description:

This is a phase II study using the combination of bortezomib, rituximab, fludarabine, mitoxantrone and dexamethasone. The combination will given over a 28 day cycle. In addition each patient will receive Pneumocystis carinii Pneumonia (PCP) prophylaxis with Trimethoprim/sulfamethoxazole (TMP/Sulfa) or equivalent agent. On day 4 the physician has the option of starting granulocyte colony-stimulating factor (GCSF), granulocyte macrophage colony-stimulating factor (GMCSF), or pegylated GCSF.

All patients who receive at least one dose of the drug will be evaluated for toxicity. Patients will be treated with the agent for at least 2 cycles to be considered eligible for evaluation of response. The chemotherapy dosing will continue until there is evidence of disease progression, a second recurrence of unacceptable toxicity, or a maximum of 8 courses of therapy.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of grade 1-3 follicular lymphoma with persistent, relapsed, or refractory disease to at least one prior regimen.
  • No prior bortezomib therapy.
  • Voluntary written informed consent.
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study therapy.
  • 18 years of age or older.
  • aspartate aminotransferase (AST),alanine aminotransferase (ALT), total bilirubin < 3 times the upper limit of normal unless documented by the treating physician to be secondary to underlying lymphoma.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

  • Platelet count of < 50,000 within 14 days before enrollment unless documented by the treating physician to be due to the disease.
  • Absolute neutrophil count of < 1000 within 14 days before enrollment unless documented by the treating physician to be due to disease.
  • Estimated or measured creatinine clearance of less than 30 ml/min within 14 days before enrollment.
  • ≥Grade 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, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia.
  • Patient has hypersensitivity to boron, mannitol or any drug included in the current protocol.
  • Female subject is pregnant or lactating.
  • Received other investigational drugs for this disease within 14 days of enrollment
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Known HIV+ status.
  • Cardiac ejection fraction less than 35% at study entry measured by echocardiogram, Multigated Acquisition (MUGA) or cardiac MRI.
  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: NCT00510887

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: David A Rizzieri, MD Duke University
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00510887     History of Changes
Other Study ID Numbers: Pro00008487, 8785
Study First Received: August 1, 2007
Results First Received: December 18, 2013
Last Updated: April 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
follicular lymphoma
Velcade
VR-FND

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Fludarabine
Fludarabine monophosphate
Rituximab
Bortezomib
Mitoxantrone
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 20, 2014