Monoclonal Antibody Therapy, Paclitaxel, and Cyclosporine in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma

University of California (UC) Davis

Status and phase: Unknown; Phase 1

Conditions: Lymphoma

Treatments: Biological: monoclonal antibody Lym-1; Radiation: yttrium Y 90 monoclonal antibody Lym-1; Radiation: indium In 111 monoclonal antibody Lym-1; Drug: paclitaxel; Drug: cyclosporine

Study type: Interventional

Funder types: Other

Identifiers

NCT00009776

CDR0000068371

NCI-V00-1641

UCD-991869

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for non-Hodgkin's lymphoma.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy combined with paclitaxel and cyclosporine in treating patients who have recurrent or refractory non-Hodgkin's lymphoma.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody Lym-1 in combination with paclitaxel and cyclosporine in patients with recurrent or refractory non-Hodgkin's lymphoma.

OUTLINE: This is a dose-escalation study of yttrium Y 90 monoclonal antibody Lym-1 (Y90 MOAB Lym-1).

Patients receive oral cyclosporine every 12 hours on days -2 to 14. Patients receive unlabeled MOAB Lym-1 IV followed by a tracer dose of indium In 111 MOAB Lym-1 IV on day 0. On day 7, patients receive unlabeled MOAB Lym-1 IV followed by Y90 MOAB Lym-1 IV. Patients in cohorts 2-4 also receive paclitaxel IV over 3 hours on day 9. Courses repeat every 8 weeks for a total of 3 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3 patients receive escalating doses of Y90 MOAB Lym-1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity.

Patients are followed monthly for 3 months, every 3 months for 21 months, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 36 months.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of non-Hodgkin's lymphoma (NHL) that has failed standard first-line chemotherapy
• Measurable disease
• NHL tissue Lym-1 reactive in vitro
• Normocellular bone marrow as evidenced by less than 25% of the bone marrow being NHL by bilateral bone marrow biopsy
• No bone marrow evidence of myelodysplastic syndrome
• HAMA titer negative

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• 3 to 6 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 130,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST no greater than 84 U/L

Renal:

• Creatinine less than 1.5 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• LVEF at least 50%

Pulmonary:

• FEV1 at least 60% of predicted
• FVC at least 60% of predicted
• DLCO at least 50%

Other:

• No other prior malignancy within the past 5 years except for nonmelanoma skin cancer
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior external beam radiotherapy

Surgery:

• Not specified