LMB-2 Immunotoxin in Treating Young Patients With Relapsed or Refractory Leukemia or Lymphoma

NCT ID: NCT00085150

Last Updated: 2015-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-30

Brief Summary

RATIONALE: LMB-2 immunotoxin can locate cancer cells and kill them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of LMB-2 immunotoxin in treating young patients with relapsed or refractory leukemia or lymphoma.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of LMB-2 immunotoxin in pediatric patients with CD-25 positive relapsed or refractory leukemia or lymphoma.
• Determine the toxic effects of this drug in these patients.
• Determine the pharmacokinetics of this drug, including the terminal elimination serum half-life, area under the curve, volume of distribution, and relationship to disease burden, in these patients.

Secondary

• Evaluate the immonogenicity of this drug in these patients.
• Determine response in patients treated with this drug.
• Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression, neutralizing antibodies (i.e., > 75% of the activity of 1 µg/mL of LMB-2 immunotoxin), or unacceptable toxicity. Patients achieving complete remission (CR) receive 2 additional courses beyond CR. Patients with acute lymphoblastic leukemia also receive cytarabine and hydrocortisone intrathecally once monthly concurrent with restaging lumbar punctures.

Cohorts of 3-6 patients receive escalating doses of LMB-2 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, a total of 12 patients are treated at that dose level.

Patients are followed weekly for 1 month and then monthly thereafter.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 2-4 years.

Conditions

Leukemia; Lymphoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

LMB-2 immunotoxin

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• No CNS leukemia or lymphoma, as evidenced by any of the following criteria:

• Cerebrospinal fluid (CSF) WBC > 5/µl AND confirmation of CSF blasts
• Cranial neuropathies secondary to underlying malignancy
• CNS lymphoma detected by radiological imaging

• Prior CNS involvement with no current evidence of CNS malignancy allowed
• No isolated testicular ALL

PATIENT CHARACTERISTICS:

Age

• 6 months to 21 years

Performance status

• ECOG 0-3 (≥ 12 years of age)
• Lansky 40-100% (< 12 years of age)

Life expectancy

• Not specified

Hematopoietic

• Pancytopenia due to disease allowed
• For patients without bone marrow involvement:

• Absolute neutrophil count > 1,000/mm^3
• Platelet count > 50,000/mm^3 (transfusion independent)

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 5 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine clearance ≥ 60 mL/min OR
• Creatinine, meeting the following age-related criteria:

• ≤ 0.8 mg/dL (≤ 5 years of age)
• ≤ 1.0 mg/dL (6 to 10 years of age)
• ≤ 1.2 mg/dL (11 to 15 years of age)
• ≤ 1.5 mg/dL (> 15 years of age)
• Calcium 2.0-2.9 mmol/L

Cardiovascular

• Ejection fraction ≥ 45% by MUGA OR
• Shortening fraction ≥ 28% by echocardiogram

Pulmonary

• Oxygen saturation ≥ 90%

Other

• Sodium 130-150 mmol/L
• Potassium 3.0-5.5 mmol/L
• Magnesium 0.5-1.23 mmol/L
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant unrelated systemic illness that would preclude study participation
• No conditions that would preclude study compliance
• No serum that neutralizes > 75% of the activity of 1 μg/mL of LMB-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse immunoglobulin G antibodies)
• No active graft-vs-host disease (i.e., off immunosuppression)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior autologous bone marrow transplantation (BMT) allowed
• At least 100 days since prior allogeneic BMT
• At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)

Chemotherapy

• At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) except intrathecal chemotherapy
• No other concurrent chemotherapy

Endocrine therapy

• Concurrent corticosteroids allowed provided the dose has been stable for the past week and does not increase during study treatment

• Tapering or discontinuation of steroids allowed

Radiotherapy

• At least 3 weeks since prior radiotherapy unless < 10% of marrow is irradiated and measurable disease exists outside the radiation port

Surgery

• Not specified

Other

• Recovered from all prior therapy
• At least 30 days since prior investigational agents
• Concurrent oral supplementation to maintain normal electrolyte levels allowed
• No concurrent anticoagulation therapy for disease-related conditions
• No other concurrent investigational agents

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Alan S. Wayne, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

Doernbecher Children's Hospital at Oregon Health & Science University

Portland, Oregon, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Other Identifiers

NCI-04-C-0168

Identifier Type: -

Identifier Source: secondary_id

NCI-5903

Identifier Type: -

Identifier Source: secondary_id

CDR0000367333

Identifier Type: -

Identifier Source: org_study_id

NCT00082004

Identifier Type: -

Identifier Source: nct_alias