Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Rituximab and Interleukin-2 in Treating Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma That is Refractory to Rituximab

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	UCLA-0302013 CHIR-IL2NHL03-A01, NCT00066534

Objectives

1. Determine the complete and partial response rate in patients with low-grade or follicular non-Hodgkin's lymphoma refractory to prior single-agent rituximab when treated with rituximab and interleukin-2.
2. Determine the safety of this regimen in these patients.
3. Determine the time to progression in patients treated with this regimen.
4. Determine the pharmacokinetics of interleukin-2 in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed B-cell non-Hodgkin's lymphoma
  • Low-grade or follicular



• CD20+ disease



• Measurable disease



• Relapsed or unresponsive disease after a single-agent course of rituximab
  • Relapsed less than 6 months after therapy
  • Prior rituximab dose at least 75% of the total standard labeled dose (standard dose is 4 weekly doses at 375 mg/m²)
  • No prior rituximab in combination with chemotherapy or another therapeutic modality (e.g., radiotherapy or radioimmunoconjugates)



• No mantle cell lymphoma or chronic lymphocytic leukemia



• No primary CNS lymphoma or lymphomatous meningitis

 [Note: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• No prior allogeneic bone marrow transplantation
  • Prior autologous peripheral blood stem cell transplantation allowed
• No prior interleukin-2
• No concurrent interferon alfa, interferon beta, or interferon gamma
• No concurrent monoclonal antibody OKT3

Chemotherapy

• See Disease Characteristics
• More than 30 days since prior chemotherapy
• No concurrent anticancer chemotherapy

Endocrine therapy

• Concurrent replacement treatment for hypothyroidism allowed
• No concurrent systemic corticosteroids

Radiotherapy

• See Disease Characteristics
• More than 30 days since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 30 days since prior major surgery

Other

• More than 6 weeks since prior experimental drugs
• No concurrent mycophenolate mofetil, cyclosporine, or tacrolimus

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,000/mm³
• Lymphocyte count less than 20,000/mm³
• Platelet count at least 75,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic

• Bilirubin no greater than 3 mg/dL
• Transaminases no greater than 2.5 times upper limit of normal
• Hepatitis B surface antigen negative
• No clinically significant hepatic dysfunction

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No clinically significant cardiac dysfunction
• No history of congestive heart failure unless stable for at least 6 months and currently asymptomatic
• No history of myocardial infraction unless stable for at least 6 months and currently asymptomatic

Pulmonary

• No clinically significant pulmonary dysfunction

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• Able and willing to administer interleukin-2 in an outpatient setting or have an available personal assistant to do so
• No history of autoimmune disease
• No symptomatic thyroid disease requiring medical intervention
• No serious, uncontrolled, active infection
• No type I hypersensitivity or anaphylactic reactions to murine proteins, prior rituximab, or radioconjugated CD20 antibody
• No other prior or concurrent malignancy except inactive nonmelanoma skin cancer, carcinoma in situ of the cervix, or other curatively treated solid tumor and without evidence of recurrence for at least 1 year

Expected Enrollment

A total of 12-150 patients will be accrued for this study.

Outline

This is an open-label, multicenter study.

Patients receive rituximab IV once weekly on weeks 1-4 and interleukin-2 subcutaneously 3 times weekly on weeks 2-9 in the absence of unacceptable toxicity.

Patients are followed every 4 weeks for approximately 1.5 years or until disease progression.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Christos Emmanouilides, MD, Principal investigator		Ph: 310-206-0716; 888-798-0719 Email: cemmanou@mednet.ucla.edu

Registry Information
Official Title		An Open-Label Phase II/III Study of Rituximab in Combination with Recombinant Human IL-2 (IL-2) for Relapsed Low-Grade or Follicular Non-Hodgkin's Lymphoma in Subjects Who Have Previously Failed Rituximab
Trial Start Date		2003-05-02
Registered in ClinicalTrials.gov		NCT00066534
Date Submitted to PDQ		2003-06-18
Information Last Verified		2004-08-19
NCI Grant/Contract Number		P30-CA16042