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

Alternate Title

Monoclonal Antibody Therapy, Chemotherapy, and Peripheral Stem Cell Transplantation in Treating Patients With Refractory Non-Hodgkin's Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Other UCD-991860 NCI-V00-1638, NCT00008021

Objectives

1. Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody Lym-1 administered with cyclosporine and paclitaxel followed by autologous peripheral blood stem cell transplantation in patients with refractory non-Hodgkin's lymphoma.
2. Determine the toxicity of this treatment regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed non-Hodgkin's lymphoma (NHL) that has failed standard therapy
  • Any grade allowed
  • Intermediate or high grade NHL must have failed standard therapy with curative intent



• Measurable disease



• HAMA titer negative



• NHL tissue Lym-1 reactive in vitro



• Bilateral bone marrow biopsy less than 25% NHL



• No evidence of myelodysplastic syndrome in bone marrow

 [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:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy involving more than 25% of bone marrow
• At least 4 weeks since prior external beam radiotherapy

Surgery:

• Not specified

Patient Characteristics:

Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 130,000/mm³

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
• Corrected DLCO at least 50%

Other:

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

Expected Enrollment

A maximum of 40 patients will be accrued for this study within 36 months.

Outline

This is an open-label, dose escalation study of yttrium Y 90 monoclonal antibody Lym-1 (Y90 MOAB Lym-1). Patients are assigned to one of four cohorts.

• Cohort I: Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 4 days prior to peripheral blood stem cell (PBSC) mobilization and continuing until adequate PBSC are collected. Patients receive unlabeled monoclonal antibody (MOAB) Lym-1 IV followed by a tracer dose of indium In 111 MOAB Lym-1 (In111 MOAB Lym-1) IV on day 0 and unlabeled MOAB Lym-1 IV followed by Y90 MOAB Lym-1 IV on day 7. Patients also receive oral cyclosporine every 12 hours on days -2 to 14. Patients may undergo autologous PBSC transplantation, if necessary, no earlier than day 17 and receive G-CSF SC beginning at the completion of PBSC re-infusion and continuing until blood counts recover.



• Cohort II: Patients undergo PBSC mobilization and receive treatment as in cohort I. Patients also receive paclitaxel IV over 3 hours on day 9.



• Cohort III: Patients undergo PBSC mobilization and receive unlabeled MOAB Lym-1, In111 MOAB Lym-1, Y90 MOAB Lym-1, and cyclosporine as in cohort I and paclitaxel as in cohort II. Patients undergo autologous PBSC transplantation no earlier than day 17. Patients receive G-CSF after transplantation as in cohort I.



• Cohort IV: Patients undergo PBSC mobilization and receive treatment as in cohort III. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 1 to 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 at which 1 of 3 patients require PBSC transplantation, or 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 1 year, every 6 months for 1 year, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

University of California Davis Cancer Center

Gerald DeNardo, MD, Protocol chair		Ph: 916-734-3787

Registry Information
Official Title		A Phase I Study of 90Y-DOTA-Peptide-Lym-1 With Peripheral Blood Stem Cell Support, Paclitaxel And Cyclosporin A In Patients With Non-Hodgkin's Lymphoma
Trial Start Date		2001-02-14
Registered in ClinicalTrials.gov		NCT00008021
Date Submitted to PDQ		2000-11-09
Information Last Verified		2002-12-06