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Retreatment Protocol for BL22 Immunotherapy in Relapsed or Refractory Hairy Cell Leukemia

Phase 2
18 Years
Not Enrolling
Hairy Cell Leukemia

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Trial Information

Retreatment Protocol for BL22 Immunotherapy in Relapsed or Refractory Hairy Cell Leukemia


BL22, also called CAT-3888 or RFB4(dsFv)-PE38, is a recombinant immunotoxin containing an Fv
fragment of an anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin (PE).

In Phase 1 and 2 trials in patients with chemoresistant hairy cell leukemia (HCL), BL22
showed 47-61% complete remission (CR) rates and 12% of HCL patients had a completely
reversible hemolytic uremic syndrome (HUS).

A mutant of BL22, termed CAT-8015 or HA22, differs by 3 amino acids and has higher binding
affinity to CD22 compared to BL22 (15-fold greater). CAT-8015 is currently undergoing Phase
1 testing in HCL and other diseases.

HCL patients who have previously received recombinant anti-CD22 immunotoxin (BL22, CAT-8015,
or LMB-2) may benefit from additional BL22 administration.


The primary objective is to provide access to BL22 for HCL patients who have previously
received BL22, CAT-8015, or LMB-2, or are ineligible for CAT-8015, but may benefit from
BL22. The primary outcome will be response to treatment.

Secondary objectives:

- Determine immunogenicity and safety profiles of BL22 in patients with prior
immunotoxin, using aspirin/enoxaparin to prevent HUS.

- To correlate response to ex vivo sensitivity of HCL cells, obtained from blood with or
without apheresis, to BL22 and to other recombinant anti-CD22 immunotoxins such as
CAT-8015, and to tumor markers.

- To correlate neutralizing antibodies with number of cycles of BL22, type and number of
prior systemic therapies, and time since prior purine analog.

- To correlate CR by bone marrow biopsy with improvement in bone marrow as assessed by
magnetic resonance imaging (MRI) of the spine.


Patient must have received prior recombinant anti-CD22 immunotoxin (i.e. BL22, CAT-8015, or
LMB-2 treatment) or be ineligible for CAT-8015.

HCL with cytopenia, high malignant count or symptomatic splenomegaly.

Patients must have had at least 2 prior systemic therapies. There must have been at least 2
prior courses of purine analog, or 1 if the response to this course lasted < 2 years, or if
the patient had unacceptable toxicity to purine analog.


This is a single institution, expanded access protocol accruing 21-25 patients.

Patients will be administered BL22 at 30 microg/kg every other day for 3 doses (QOD times 3)
per 4-week cycle (at least 26 days) for a maximum of 16 cycles.

Patients in CR may receive up to 2 more cycles if without minimal residual disease (MRD), or
4 more cycles if in CR with MRD, but no more than 16 cycles total.

No retreatment if high levels of neutralizing antibodies or progressive disease.

Patients who have been off treatment and relapse after greater than 2 months of a CR or
partial response may be retreated if eligibility criteria are still met.

If any HUS, accrual to the study will be suspended for discussion with FDA.

Inclusion Criteria


One of the following:

1. Patients who previously received CAT-3888 and did not have unacceptable toxicity

2. Patients who received CAT 8015 in study CAT 8015-1001 and have progression of disease
or relapse. These patients must be considered off-study for CAT-8015 protocol
specified follow-up

Patient must have histopathological evidence of HCL as confirmed by the Laboratory of
Pathology, NCI.

At least one of the following indications for treatment:

1. Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microL).

2. Anemia (hemoglobin (Hgb) less than 10 g/dL).

3. Thrombocytopenia (platelet (Plt) less than 100,000/microL).

4. Absolute lymphocyte count of greater than 5000 cells/microL

5. Symptomatic splenomegaly.

6. Enlarging lymph nodes greater than 2cm.

Patient must have had at least 2 prior systemic therapies. There must have been at least 2
prior courses of purine analog, or 1 if the response to this course lasted less than 2
years, or if the patient had unacceptable toxicity to purine analog.

Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2,
unless due to potentially reversible active uncontrolled infection.

Patient must be greater than or equal to 18 years old.

Patient can understand and give informed consent.

Patient must have adequate liver and renal function, as defined by the following criteria:

1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or
equal to 2.5-times the upper limits of normal.

2. Albumin greater than or equal to 3.0 g/dL.

3. Total bilirubin less than or equal to 2.2 mg/dL.

4. Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than or
equal to 50 mL/min.

Patient must agree to using adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry and for the duration of the study.


Patients who are pregnant or nursing. A negative pregnancy test (urine or serum) must be
documented within one week prior to starting BL22 in women of child-bearing potential.

Patient has developed antibody titer that neutralizes greater than 75% of the activity of
1 microg/mL of BL22 using a bioassay.

Patients who had systemic cytotoxic chemotherapy, immunotherapy, recombinant anti-CD22
immunotoxin (ie, CAT-8015, BL22, or LMB-2) or systemic steroid (with the exception of
stable doses of Prednisone less than or equal to 20 mg/day) treatment within 4 weeks of
enrollment. Patients receiving a limited number of doses (less than 5) of steroid for
non-treatment reasons (eg, allergy prophylaxis connected with medical testing) may not
receive any steroid within one week of enrollment and may not have had any evidence of
disease response to steroid. Subjects who are receiving steroids for other conditions
(e.g., autoimmune disorders) are eligible, as long as there is no increase in the dose or
change in steroid type within 1 week of treatment. Subjects who are using a chronic
steroid must wait for 4 weeks before starting the trial.

Patient had monoclonal antibody therapy (with the exception of BL22 or CAT-8015 or LMB-2)
within 4 weeks of enrollment.

Patient is receiving any other investigational agent.

Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements.

Patients who discontinued from CAT-8015 or BL22 studies due to toxicity or dose-limiting

Dose limiting toxicity to CAT-8015

Type of Study:


Study Design:

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

Outcome Measure:

Number of Months to Response to Treatment

Outcome Description:

Response is defined by the Response Evaluation Criteria in the protocol, namely the earliest point where all relevant tests (i.e. lab tests, physical exam, radiology results) are consistent with complete response (CR) or partial response (PR). CR or PR must be confirmed for at least 4 weeks. Complete response: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. Partial response:neutrophils >/= 1,500/micrograms/L or 50% improvement over baseline without growth factors for at least 4 weeks.

Outcome Time Frame:

2/14/2009 till 6/24/2010

Safety Issue:


Principal Investigator

Robert J Kreitman, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute, National Institutes of Health


United States: Federal Government

Study ID:




Start Date:

February 2009

Completion Date:

August 2010

Related Keywords:

  • Hairy Cell Leukemia
  • BL22 in HCL after Immunotoxin
  • Hairy Cell Leukemia
  • Leukemia
  • Leukemia
  • Leukemia, Hairy Cell



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892