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

Lymphoma Clinical Trial

Official title:

Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085150
• Other study ID #: CDR0000367333
• Secondary ID: NCI-04-C-0168NCI
• Status: Completed
• Phase: Phase 1
• First received: June 10, 2004
• Last updated: April 29, 2015
• Start date: April 2004

Study information

• Verified date: February 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00082004

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed diagnosis of 1 of the following:

• Non-Hodgkin's lymphoma, including the following subtypes:

• Lymphoblastic lymphoma

• Burkitt's lymphoma

• Large cell lymphoma

• Adult T-cell leukemia/lymphoma

• Cutaneous T-cell lymphoma

• Peripheral T-cell lymphoma

• Hodgkin's disease

• Acute myeloid leukemia

• Chronic myelogenous leukemia

• Acute lymphoblastic leukemia (ALL)

• More than 5% blasts in the bone marrow (i.e., M2 marrow classification)

• Acute hybrid leukemia, including the following subtypes:

• Mixed lineage leukemia

• Biphenotypic leukemia

• Undifferentiated leukemia

• CD25-positive (CD25+) disease, meeting 1 of the following criteria:

• More than 15% of malignant cells are CD25+ by immunohistochemistry with anti-CD25 antibody

• More than 30% of malignant cells from a site are CD25+ by fluorescence-activated cell sorting analysis

• Measurable or evaluable disease

• Relapsed or refractory disease after at least 1 standard chemotherapy regimen AND 1 salvage regimen

• No available alternative curative therapies

• Ineligible for or refused hematopoietic stem cell transplantation OR disease activity that prohibits the required time to identify a suitable stem cell donor

• 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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma

Intervention

Biological:
• LMB-2 immunotoxin

Locations

Country	Name	City	State
United States	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	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Doernbecher Children's Hospital at Oregon Health & Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,