Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma

This study has been terminated.
(Slow accrual)
Sponsor:
Collaborators:
Genentech
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT01186458
First received: August 19, 2010
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to determine the effectiveness of fludarabine, Velcade, and rituximab treatment regimen in patients with relapsed or refractory follicular non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: Fludarabine
Drug: Velcade
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma: Hoosier Oncology Group LYM08-134

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To determine the overall response rate and frequency of complete and partial responses in patients with relapsed or refractory follicular non-Hodgkin lymphoma (NHL) who receive therapy with fludarabine, Velcade, and rituximab administered every 28 days.


Secondary Outcome Measures:
  • Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab.

  • Toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    To evaluate the toxicity profile of this regimen.

  • Biologic Interaction [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine.


Enrollment: 4
Study Start Date: October 2010
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine, Velcade and Rituximab
Fludarabine, Velcade and Rituximab
Drug: Fludarabine
Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.
Drug: Velcade
Velcade (given after fludarabine)1.3 mg/m2 IV push over 3 to 5 seconds on days 1, 4, 8, 11. Cycle = 28 days; maximum of 6 cycles of therapy.
Drug: Rituximab
Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy.

Detailed Description:

OUTLINE: This is a multi-center study.

  • Fludarabine 25 mg/m2 IV over 30 minutes , Days 1, 2, 4
  • Velcade(given after fludarabine) 1.3 mg/m2 IV push over 3 to 5 seconds, Days 1, 4, 8, 11
  • Rituximab (given after Velcade) 375 mg/m2 IV piggyback, Day 1
  • Cycle = 28 days; max 6 cycles

ECOG Performance Status: 0-2

Life Expectancy: Not specified

Hematopoietic:

  • Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (ANC > 0.5 K/mm3 if known lymphomatous involvement of the bone marrow).
  • Platelets ≥ 100 K/mm3 (Platelets >50 K/mm3 if known lymphomatous involvement of the bone marrow).

Hepatic:

  • Total bilirubin ≤1.5 ULN
  • Aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN
  • Alanine aminotransferase (ALT, SGPT) ≤ 2.5 x ULN

Renal:

  • Creatinine < 1.5 x institutional upper limit (ULN) or creatinine clearance ≥ 50 cc/min

Cardiovascular:

  • No myocardial infarction within 6 months prior to enrollment
  • No heart failure per New York Heart Association Classification III or IV
  • No severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia
  Eligibility

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

Inclusion Criteria:

  • Must have histologically confirmed Follicular Non-Hodgkin Lymphoma (Grade I, II, or IIIa)
  • Must have measurable disease defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥2 cm with conventional techniques or as >1 cm with spiral CT scan) and obtained by imaging within 30 days prior to registration for protocol therapy.
  • Must have received at least one prior therapeutic regimen, but no more than three prior regimens of conventional cytotoxic therapy. NOTE: Prior recipients of stem cell transplantation will be included, with the preparative cytoreductive and high-dose therapies counted collectively as one prior therapy.
  • Must be off all cytotoxic chemotherapy for at least four weeks prior to registration for protocol therapy (6 weeks for BCNU or mitomycin C).
  • Patients are allowed to have received one course of prior radioimmunotherapy (RIT: either tositumomab or ibritumomab). NOTE: Radioimmunotherapy must be completed at least 12 weeks prior to registration for protocol therapy with recovery to baseline of ANC and platelets.
  • Prior fludarabine, Velcade or rituximab is allowed as long as therapy is completed at least 30 days prior to registration for protocol therapy. Patients may be refractory (defined as not responding or demonstrating progressive disease in <6 months) to prior rituximab. Patients may not be refractory to prior fludarabine or Velcade.
  • Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed and for 30 days following protocol therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to prior to registration for protocol therapy. NOTE: Patients are considered of child bearing potential unless they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal (no menses for at least 12 months).
  • Females must not be breastfeeding.
  • Males must agree to use an acceptable method of contraception for the duration of the study.

Exclusion Criteria:

  • No current active CNS metastases. Patients with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis within 7 days prior to registration for protocol therapy. NOTE: Patients with treated brain metastasis must be off steroids or on tapering or stable doses of steroids and have completed radiation at least 30 days prior to registration for protocol therapy.
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, Gleason ≤ grade 6 prostate cancers, or other cancer for which the subject has been disease-free for at least 3 years.
  • No treatment with any investigational agent within 30 days prior to registration for protocol therapy.
  • Prior radiation therapy is allowed to < 25% of the bone marrow. NOTE: No radiation therapy within 30 days prior to registration for protocol therapy.
  • No clinically significant infections as judged by the treating investigator.
  • No active HIV, hepatitis B or hepatitic C infection.
  • No cerebrovascular accident (CVA) within 6 months of study enrollment.
  • No psychiatric illness/social situations that would limit compliance with study requirements.
  • No history of hypersensitivity to Velcade, boron or mannitol.
  • No peripheral neuropathy grade > 1.
  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: NCT01186458

Locations
United States, Indiana
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States, 47403
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
United States, New Jersey
Virtua Health Cancer Program
Mount Holly, New Jersey, United States, 08060
South Jersey Health Care
Vineland, New Jersey, United States, 08360
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Case Comprehensive Cancer Center - University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106
Seidman Cancer Center
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Reading Hospital Regional Cancer Center
W. Reading, Pennsylvania, United States, 19611
Sponsors and Collaborators
Hoosier Cancer Research Network
Genentech
Millennium Pharmaceuticals, Inc.
Investigators
Study Chair: Shivani Srivastava, M.D. Hoosier Cancer Research Network
  More Information

Additional Information:
No publications provided

Responsible Party: Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT01186458     History of Changes
Other Study ID Numbers: HOG LYM08-134
Study First Received: August 19, 2010
Last Updated: March 19, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Fludarabine
Fludarabine phosphate
Rituximab
Bortezomib
Vidarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014