Anti-Tac(Fv)-PE38 (LMB-2) to Treat Cutaneous T-Cell Lymphomas

NCT00080535 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 04014204-C-0142
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effectiveness of an experimental drug called LMB-2 for treating cutaneous T-cell lymphoma in patients who have a protein called cluster of differentiation 25 (CD25) on their cancer cells. LMB-2 is a recombinant immunotoxin. It is made up of two parts: a genetically engineered monoclonal antibody that binds to CD25, and a toxin produced by bacteria that kills the cancer cells to which it binds. LMB-2 has killed CD25-containing cells in laboratory experiments and has caused tumors in mice to shrink. Preliminary studies in humans have shown some effectiveness in shrinking tumors in patients with various types of lymph and blood cancers. Patients 18 years of age and older with stage 1b to IV cutaneous T-cell lymphoma that has progressed within 2 years of systemic or topical therapy and who have CD25 receptor proteins on their cancer cells may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), echocardiogram, chest x-ray, computed tomography (CT) scans of the chest, abdomen and pelvis, skin punch biopsy to evaluate tumor infiltration in the skin, and a bone marrow biopsy on patients with stage IIa disease and higher. In addition, the patient's blood, bone marrow, tumor, or other tissue is tested to determine the presence of CD25 on cancer cells. Participants receive up to nine cycles of LMB-2 therapy as long as their cancer does not worsen and they do not develop serious side effects. Each 28-day cycle consists of 30-minute infusions of LMB-2 on cycle days 1, 3, and 5. The drug is infused through an intravenous (IV) catheter (plastic tube placed in a vein) or a central venous line - an IV tube placed in a large vein in the neck or chest that leads to the heart. In addition to drug therapy, patients undergo the following procedures: Blood draws: Blood is drawn before, during, and after each LMB-2 infusion to measure blood levels of the drug, evaluate its effects on the cancer cells, and monitor side effects. Blood tests are also done before and during each cycle to determine how the immune system is interacting with the drug. Disease evaluations: Patients undergo a careful skin examination, blood tests, chest x-ray, and EKG before each treatment cycle and at follow-up visits. A CT scan and echocardiogram (heart ultrasound) are done before the first cycle. Before the first and second cycles, patients have a biopsy of the lymphoma on the skin. If the biopsy is helpful in evaluating the disease response to LMB-2, additional biopsies may be requested prior to other cycles as well. A nuclear medicine scan may be done, and a bone marrow biopsy may be done in patients with stage II to IV disease. If these tests are helpful in understanding the response of the lymphoma to treatment, they may also be repeated prior to other cycles, with the patient's permission. Patients are admitted to the National Institutes of Health (NIH) Clinical Center for the first treatment cycle. Subsequent cycles are given as outpatients. If the infusions are well tolerated, patients may return home after about one week (or possibly longer if complications occur). After returning home, patients have blood tests done weekly by their local physicians.

Conditions

Lymphoma; T-Cell; Cutaneous

Keywords

LMB-2; Cutaneous T Cell Lymphoma; CTCL; Immunotoxin; Oncology

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Response is assessed by the International Workshop's Response Criteria (IWRC) for Non-Hodgkin's Lymphomas which favors the sum of the bidimensional products for tumor measurements. Complete response is no evidence of disease. Complete response unconfirmed (CRu) is a complete response in every category except CRu in lymph nodes. Partial response is a partial response in every measurable category with non-progressive disease elsewhere. Progressive disease is progressive disease in every category. Stable disease is neither partial response nor progressive disease. For additional details about the IWRC see the protocol link module.

  Patients were followed for at least 30 days after last treatment. Because the protocol allows 6 treatment cycles, this can be up to 7 months.

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  Date treatment consent signed to date off study, approximately 6 years, 8 months and 17 days.

Study Arms (1)

LMB-2 for cutaneous Tcell lymphoma

EXPERIMENTAL

30 micrograms/kg every other day (QOD) x 3 every 4 weeks in patients with cutaneous T-cell lymphoma, a group of lymphoproliferative disorders characterized by malignant CD4+ T-lymphocytes which localize tot he skin on initial presentation.

Biological: LMB-2

Interventions

LMB-2 BIOLOGICAL

30 micrograms/kg every other day (QOD) x 3 every 4 weeks

LMB-2 for cutaneous Tcell lymphoma

Eligibility Criteria

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

You may qualify if:

• Patients must have histopathological evidence of cluster of differentiation 25 (CD25) + cutaneous T-cell lymphoma (CTCL) confirmed by the National Institutes of Health (NIH) pathology department.
• One of the following must be present:
• Greater than or equal to 20 percent expression of CD25 on the lymphocytes in the skin at a site of a patch, plaque, or tumor.
• Greater than or equal to 20 percent of the peripheral blood Sezary cells must be CD25+.
• Measurable stage Ib-IV disease that has progressed after at least 2 prior systemic or topical therapies.
• Patients must have a Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 and be at least 18 years old.
• Patients must be able to understand and give informed consent.
• Patients must be 4 weeks from any monoclonal antibodies.
• Patients must be greater than or equal to 3 weeks from any CTCL-specific therapy and have evidence of progressive disease.
• Patients who are on chronic steroids must be on a stable dose of Prednisone less than or equal to 20 mg/day (or equivalent dose of another steroid) for at least 3 weeks and have evidence of progressive disease.
• Female patients of childbearing potential must have a negative pregnancy test and must use effective contraception (a barrier form of contraception).
• The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must each be less than or equal to 2.5-times the upper limits of normal.
• Albumin must be greater than or equal to 3.0 gm/dL.
• Total bilirubin must be less than or equal to 2.2 mg/dL.
• The creatinine must be less than or equal to 2.0 mg/dL or the creatinine clearance must be greater than or equal to 50 ml/min.

You may not qualify if:

• Patients whose serum neutralizes LMB-2 in tissue culture, due either to anti-toxin or anti-mouse-IgG antibodies.
• No patient whose serum neutralizes greater than 75 percent of the activity of 1 microg/mL of LMB-2 will be treated.
• Patients who are pregnant or breast-feeding.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,
• symptomatic congestive heart failure,
• unstable angina pectoris,
• cardiac arrhythmia,
• or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are human immunodeficiency virus (HIV) positive,
• hepatitis B antigen positive,
• hepatitis C polymerase chain reaction (PCR) positive,
• or who have other chronic liver disease.
• Patients with symptomatic cardiac or pulmonary disease.
• Patients on warfarin therapy.
• Such patients may be eligible if they can be switched to heparin or low-molecular weight heparin therapy and are off warfarin at least 4 days prior to study enrollment.

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 (4)

• Siegel RS, Pandolfino T, Guitart J, Rosen S, Kuzel TM. Primary cutaneous T-cell lymphoma: review and current concepts. J Clin Oncol. 2000 Aug;18(15):2908-25. doi: 10.1200/JCO.2000.18.15.2908.

  PMID: 10920140 BACKGROUND

• Diamandidou E, Cohen PR, Kurzrock R. Mycosis fungoides and Sezary syndrome. Blood. 1996 Oct 1;88(7):2385-409. No abstract available.

  PMID: 8839829 BACKGROUND

• Weinstock MA, Horm JW. Mycosis fungoides in the United States. Increasing incidence and descriptive epidemiology. JAMA. 1988 Jul 1;260(1):42-6.

  PMID: 3379722 BACKGROUND

• Matsushita K, Margulies I, Onda M, Nagata S, Stetler-Stevenson M, Kreitman RJ. Soluble CD22 as a tumor marker for hairy cell leukemia. Blood. 2008 Sep 15;112(6):2272-7. doi: 10.1182/blood-2008-01-131987. Epub 2008 Jul 2.

  PMID: 18596230 DERIVED

Related Links

• International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas

MeSH Terms

Conditions

Lymphoma; Lymphoma, T-Cell, Cutaneous; Neoplasms

Interventions

B3(Fv)-PE38KDEL recombinant immunotoxin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin

Results Point of Contact

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

kreitmar@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: April 7, 2004
• First Posted: April 7, 2004
• Study Start: April 30, 2004
• Primary Completion: December 31, 2011
• Study Completion: December 31, 2011
• Last Updated: January 29, 2018
• Results First Posted: October 24, 2012

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)