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BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00077493
Recruitment Status : Suspended (protocol development and Amended protocol revision)
First Posted : February 12, 2004
Last Update Posted : December 28, 2007
Sponsor:
Collaborator:
Cambridge Antibody Technology
Information provided by:
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE February 10, 2004
First Posted Date  ICMJE February 12, 2004
Last Update Posted Date December 28, 2007
Study Start Date  ICMJE January 2004
Estimated Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
assessment of efficacy, safety, pharmacokinetics, immunogenicity. [ Time Frame: end of study ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00077493 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Expansion of MTD [ Time Frame: end of study ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Non-Hodgkin's Lymphoma
Official Title  ICMJE Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Lymphoma
Intervention  ICMJE
  • 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.
  • Procedure: antibody-drug conjugate therapy
    CD22 antibody, RFB4 on day 7
  • Procedure: immunotoxin therapy
    tested for immunogenicity to CAT-8015 before each cycle and at end of study.
  • Procedure: monoclonal antibody therapy
    administered intravenously over 30 minutes.
Study Arms  ICMJE
  • Active Comparator: 1
    BL22 immunotoxin
    Intervention: Drug: BL22 immunotoxin
  • Active Comparator: 2
    antibody therapy
    Intervention: Procedure: antibody-drug conjugate therapy
  • Active Comparator: 3
    immunotoxin therapy
    Intervention: Procedure: immunotoxin therapy
  • Active Comparator: 4
    monoclonal antibody therapy
    Intervention: Procedure: monoclonal antibody therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: February 15, 2007)
95
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE October 2008
Estimated Primary Completion Date October 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00077493
Other Study ID Numbers  ICMJE CDR0000352020
NCI-04-C-0079H
NCI-5643
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Karen Kaucic, M.D., MedImmune Inc.
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Cambridge Antibody Technology
Investigators  ICMJE
Principal Investigator: Alan S. Wayne, MD National Cancer Institute (NCI)
PRS Account MedImmune LLC
Verification Date December 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP