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

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

A Phase II Study of Fludarabine, Velcade and Rituximab for Relapsed or Refractory Follicular Non-Hodgkin Lymphoma: Hoosier Oncology Group LYM08-134

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01186458
• Other study ID #: HOG LYM08-134
• Status: Terminated
• Phase: Phase 2
• First received: August 19, 2010
• Last updated: August 22, 2016
• Start date: October 2010
• Est. completion date: October 2013

Study information

• Verified date: August 2016
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Fludarabine
Fludarabine 25 mg/m2 IV over 30 minutes on days 1, 2, 4. Cycle = 28 days; maximum of 6 cycles of therapy.
• 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.
• Rituximab
Rituximab given after Velcade) 375 mg/m2 IV piggyback on day 1. Cycle = 28 days; maximum of 6 cycles of therapy.

Locations

Country	Name	City	State
United States	Cancer Care Center of Southern Indiana	Bloomington	Indiana
United States	Case Comprehensive Cancer Center - University Hospitals Case Medical Center	Cleveland	Ohio
United States	Seidman Cancer Center	Cleveland	Ohio
United States	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana
United States	Community Regional Cancer Center	Indianapolis	Indiana
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Arnett Cancer Care	Lafayette	Indiana
United States	Virtua Health Cancer Program	Mount Holly	New Jersey
United States	University of Rochester Medical Center	Rochester	New York
United States	South Jersey Health Care	Vineland	New Jersey
United States	Reading Hospital Regional Cancer Center	W. Reading	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Genentech, Inc., Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	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.	6 months	No
Secondary	Survival	To evaluate the progression-free survival and event-free survival in patients who receive therapy with fludarabine, Velcade, and rituximab.	6 months	No
Secondary	Toxicity	To evaluate the toxicity profile of this regimen.	6 months	Yes
Secondary	Biologic Interaction	To explore the biologic interaction between fludarabine and Velcade and determine if Velcade can potentiate the DNA-damaging effect of fludarabine.	6 months	No

External Links

•   Hoosier Oncology Group Homepage