Protocol Number: 09-C-0076

Title:

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

Number:

09-C-0076

Summary:

Background:

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.

Objectives:

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.

Eligibility:

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.

Design:

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 x 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.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

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 (ANC less than 1000 cells/microL).

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

3. Thrombocytopenia (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 les than 2 years, or if the patient had unacceptable toxicity to purine analog.

Patient must have 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. ALT and 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.

EXCLUSION CRITERIA:

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 toxicity.

Dose limiting toxicity to CAT-8015

Special Instructions:

Currently Not Provided

Keywords:

BL22 in HCL after Immunotoxin

Recruitment Keyword(s):

Hairy Cell Leukemia

Leukemia

Condition(s):

Hairy Cell Leukemia

Investigational Drug(s):

CAT 3888/IND 8099 (BL22)

Investigational Device(s):

None

Intervention(s):

Drug: BL22 (CAT-3888)

Drug: CAT 3888/IND 8099 (BL22)

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood. 1958 Jul;13(7):609-30.

Frassoldati A, Lamparelli T, Federico M, Annino L, Capnist G, Pagnucco G, Dini E, Resegotti L, Damasio EE, Silingardi V. Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. Leuk Lymphoma. 1994 Apr;13(3-4):307-16.

Vardiman JW, Golomb HM. Autopsy findings in hairy cell leukemia. Semin Oncol. 1984 Dec;11(4):370-80.

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