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

NCT00924040 | Terminated Phase 2 Results

• 2 other identifiers: 09007609-C-0076
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

BL22 is a type of protein that scientists have created to interact with certain cancer cells. Experiments have shown that BL22 can bind with cancer cells that have a particular kind of protein (called CD22 ) on their surface, and can kill those cells. CD22 is present on certain types of hairy cell leukemia (HCL) cancer cells, and researchers have been working on treatments that will use BL22 and other related proteins to interact with and kill these kinds of cancer cells. The primary purpose of this study will be to provide access to and treatment with BL22 for patients who have HCL in order to determine their response to the treatment. In addition, the study will assess potential side effects of BL22 and examine why some patients respond better than others to treatment with BL22 and related therapies. This study will include about 21 to 25 adults who have been diagnosed with forms of HCL that have not responded well to standard treatments such as surgery, chemotherapy, or radiation therapy. These adults also will have received anti-CD22 therapies before, potentially including treatments with BL22, and have not developed immunity or resistance to these treatments. Prior to the study, patients will undergo a 1- to 2-week screening period to assess their eligibility for treatment. Eligible patients will participate in the study for up to 16 cycles of treatment, with each cycle lasting approximately 4 weeks. For each cycle, patients will receive 1 prescribed dose of BL22 every other day for a total of 3 doses per cycle, and will be assessed after every cycle to evaluate the success of the treatment. During the evaluation visits, patients will be required to have a brief physical examination, give blood and urine samples for testing, and undergo other tests as need to check heart and kidney function and assess the state of the leukemia. Patients who agree will give additional blood, urine, or bone marrow samples for future research purposes.

Conditions

Hairy Cell Leukemia

Keywords

BL22 in HCL after Immunotoxin; Hairy Cell Leukemia; Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (8)

• Number of Participants With Adverse Events

  2 years & 6 months

• Number of Participants With Complete Response (CR) Who Resolve the Bone Marrow Abnormality by Magnetic Resonance Imaging (MRI)

  Bone marrow biopsy and MRI 4 weeks after patients meeting blood criteria for CR, and if CR is present, repeat bone marrow biopsy and MRI every 12 months. Bone marrow biopsy and MRI is not done in patients with PR as best response.

• Number of Patients Who Developed Neutralizing Antibodies After One or More Cycles of BL22

  24 weeks

• Number of Patients With ex Vivo Sensitivity Who Respond Clinically

  Time to CR can be between 2 months and 1 year

• Percentage of Patients Who Respond Clinically, Who Also Have Normalization in sCD22 or sCD25

  patients may undergo lymphapheresis before the first and/or later cycles up to 12 months after achieving CR or PR

Study Arms (1)

BL22 Immunotherapy

EXPERIMENTAL

30 micrograms/kg intravenous over 30 minutes every other day (QOD) on days 1, 3, 5, of a 4 week cycle (at least 26 days) for a maximum of 16 cycles or until they become ineligible.

Drug: BL22 (CAT-3888)

Interventions

BL22 (CAT-3888) DRUG

30 micrograms/kg intravenous over 30 minutes every other day (QOD) on days 1, 3, 5, of a 4 week cycle (at least 26 days) for a maximum of 16 cycles or until they become ineligible.

BL22 Immunotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of the following:
• Patients who previously received CAT-3888 and did not have unacceptable toxicity
• 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:
• Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microL).
• Anemia (hemoglobin (Hgb) less than 10 g/dL).
• Thrombocytopenia (platelet (Plt) less than 100,000/microL).
• Absolute lymphocyte count of greater than 5000 cells/microL
• Symptomatic splenomegaly.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• BOURONCLE BA, WISEMAN BK, DOAN CA. Leukemic reticuloendotheliosis. Blood. 1958 Jul;13(7):609-30. No abstract available.

  PMID: 13560561 BACKGROUND

• 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. doi: 10.3109/10428199409056295.

  PMID: 7519510 BACKGROUND

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

  PMID: 6505704 BACKGROUND

Related Links

• Medline Plus
• United States Food and Drug Administration Resources
• CTCAE

MeSH Terms

Conditions

Leukemia, Hairy Cell; Leukemia

Interventions

RFB4(dsFv)-PE38 recombinant immunotoxin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study of BL22 has expired and MedImmune, the sponsor, is not interested in producing any new supply. All data has been analyzed and reviewed. All patients have been taken off study.

Results Point of Contact

• Title: Robert J. Kreitman, M.D.
• Organization: National Cancer Institute, National Institutes of Health

kreitman@mail.nih.gov

301-496-6947

Study Officials

• Robert J Kreitman, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 18, 2009
• Study Start: February 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: October 29, 2015
• Results First Posted: May 1, 2012

Record last verified: 2015-10

Locations

US (1)