Clinical trial NCT00009776: Monoclonal Antibody Therapy, Paclitaxel, and Cyclosporine in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma
Official title: Combined Modality Radioimmunotherapy For Non-Hodgkin's Lymphoma With Three Cycles Of 90Y-DOTA-peptide-Lym-1, Paclitaxel and Cyclosporin A
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Gerald L. DeNardo, MD
role: STUDY_CHAIR
References: