Full Text View
Tabular View
No Study Results Posted
Related Studies
BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
This study has been suspended.
( protocol development and Amended protocol revision )
First Received: February 10, 2004   Last Updated: December 21, 2007   History of Changes
Sponsors and Collaborators: MedImmune LLC
Cambridge Antibody Technology
Information provided by: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00077493
  Purpose

RATIONALE: BL22 immunotoxin can locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin's lymphoma.


Condition Intervention Phase
Leukemia
Lymphoma
Drug: BL22 immunotoxin
Procedure: antibody-drug conjugate therapy
Procedure: immunotoxin therapy
Procedure: monoclonal antibody therapy
Phase I

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety Study
Official Title: Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • assessment of efficacy, safety, pharmacokinetics, immunogenicity. [ Time Frame: end of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Expansion of MTD [ Time Frame: end of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 95
Study Start Date: January 2004
Estimated Study Completion Date: October 2008
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Active Comparator
BL22 immunotoxin
Drug: BL22 immunotoxin
BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
2: Active Comparator
antibody therapy
Procedure: antibody-drug conjugate therapy
CD22 antibody, RFB4 on day 7
3: Active Comparator
immunotoxin therapy
Procedure: immunotoxin therapy
tested for immunogenicity to CAT-8015 before each cycle and at end of study.
4: Active Comparator
monoclonal antibody therapy
Procedure: monoclonal antibody therapy
administered intravenously over 30 minutes.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the toxic effects of BL22 immunotoxin in pediatric patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
  • Determine the maximum tolerated dose of this drug in these patients.
  • Determine the immunogenicity of this drug in these patients.
  • Determine the pharmacokinetics of this drug in these patients.

Secondary

  • Determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia.
  • Determine the therapeutic efficacy of this drug in inducing remissions in these patients.
  • Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.

OUTLINE: This is a non-randomized, dose-escalation study.

Patients receive BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11.

Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.

Cohorts of 3-6 patients receive escalating doses of BL22 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, the cohort is expanded and a total of 12 patients are treated at that dose.

Patients are followed weekly for at least 1 month and then every 1-3 months thereafter.

PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   6 Months to 24 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma)

    • Not amenable to available curative therapies
  • Relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen
  • CD22 positive according to at least 1 of the following criteria:

    • More than 15% CD22-positive malignant cells by immunohistochemistry
    • More than 30% CD22-positive malignant cells by fluorescent-activated cell sorter analysis
  • Measurable or evaluable disease
  • Prior CNS involvement allowed provided there is no current evidence of CNS malignancy
  • No CNS leukemia or lymphoma as manifested by any of the following:

    • Cerebrospinal fluid (CSF) WBC ≥ 5/mm^3 and confirmation of CSF blasts
    • Cranial neuropathies secondary to underlying malignancy
    • Radiologically detected CNS lymphoma
  • No isolated testicular ALL
  • Ineligible for or refused hematopoietic stem cell transplantation OR has disease activity that prohibits the time required to identify a suitable stem cell donor

PATIENT CHARACTERISTICS:

Age

  • 6 months to 24 years

Performance status

  • ECOG 0-3 (12 to 24 years of age)
  • Lansky 40-100% (under 12 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics
  • Absolute neutrophil count > 1,000/mm^3 *
  • Platelet count > 50,000/mm^3 * NOTE: *Non-leukemic patients only

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • AST and ALT ≤ 5 times upper limit of normal
  • No active hepatitis B or C infection

Renal

  • Creatinine normal for age OR
  • Creatinine clearance ≥ 60 mL/min

Immunologic

  • No serum neutralization of more than 75% of the activity of 1 µg/mL of study drug
  • HIV negative

Other

  • 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 other significant organ dysfunction that would preclude study participation
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics
  • At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
  • Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) allowed
  • More than 100 days since prior allogeneic HSCT

Chemotherapy

  • See Disease Characteristics
  • At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)

Endocrine therapy

  • Concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry

    • Steroid taper allowed

Radiotherapy

  • At least 3 weeks since prior radiotherapy

    • Allowed in the past 3 weeks provided the volume of the bone marrow treated is < 10% AND the patients has measurable disease outside of the radiation port

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • At least 30 days since prior investigational drugs
  • No other concurrent investigational drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00077493

Locations
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
MedImmune LLC
Cambridge Antibody Technology
Investigators
Principal Investigator: Alan S. Wayne, MD NCI - Pediatric Oncology Branch
  More Information

Additional Information:
No publications provided

Responsible Party: MedImmune Inc. ( Karen Kaucic, M.D. )
Study ID Numbers: CDR0000352020, NCI-04-C-0079H, NCI-5643
Study First Received: February 10, 2004
Last Updated: December 21, 2007
ClinicalTrials.gov Identifier: NCT00077493     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
recurrent childhood acute lymphoblastic leukemia
Burkitt lymphoma
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
childhood non-Hodgkin lymphoma

Study placed in the following topic categories:
Acute Lymphoblastic Leukemia, Childhood
Leukemia, Lymphoid
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immunologic Factors
Lymphoblastic Lymphoma
Immunotoxins
Recurrence
Antibodies, Monoclonal
Lymphoma, Small Cleaved-cell, Diffuse
Burkitt's Lymphoma
Leukemia
Lymphatic Diseases
Antibodies
Burkitt Lymphoma
Lymphoma, Large-cell
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Acute Lymphoblastic Leukemia
Immunoglobulins
Non-Hodgkin Lymphoma, Childhood

Additional relevant MeSH terms:
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Immune System Diseases
Physiological Effects of Drugs
Pharmacologic Actions
Immunotoxins
Antibodies, Monoclonal
Leukemia
Lymphatic Diseases
Neoplasms
Antibodies
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma
Immunoglobulins

ClinicalTrials.gov processed this record on August 30, 2009