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.
- 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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Months to Response to Treatment
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.
2/14/2009 till 6/24/2010
Robert J Kreitman, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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