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Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas

Phase 1
6 Months
24 Years
Not Enrolling
Leukemia, Lymphoma

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Trial Information

Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas



- 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.


- 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

- 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

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.

Inclusion Criteria


- 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

- 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

- 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



- 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


- See Disease Characteristics

- Absolute neutrophil count > 1,000/mm^3 *

- Platelet count > 50,000/mm^3 * NOTE: *Non-leukemic patients only


- Bilirubin ≤ 2.0 mg/dL

- AST and ALT ≤ 5 times upper limit of normal

- No active hepatitis B or C infection


- Creatinine normal for age OR

- Creatinine clearance ≥ 60 mL/min


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

- 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

- No other significant organ dysfunction that would preclude study participation

- No psychiatric illness or social situation that would preclude study compliance


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


- 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


- 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


- Not specified


- Recovered from prior therapy

- At least 30 days since prior investigational drugs

- No other concurrent investigational drugs

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

assessment of efficacy, safety, pharmacokinetics, immunogenicity.

Outcome Time Frame:

end of study

Safety Issue:


Principal Investigator

Alan S. Wayne, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

January 2004

Completion Date:

October 2008

Related Keywords:

  • Leukemia
  • Lymphoma
  • recurrent childhood acute lymphoblastic leukemia
  • Burkitt lymphoma
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • childhood non-Hodgkin lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182