Alemtuzumab (Campath) to Treat T-Large Granular Lymphocyte Leukemia

NCT00345345 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 06019006-H-0190
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the use of alemtuzumab (Campath) in patients with T cell large granular lymphocytic leukemia (T-LGL). Patients with T-LGL often have reduced white blood cells, red blood cells and platelets, and increased numbers of abnormal cells called large granular lymphocytes (LGLs). Patients may have recurrent infections, anemia, or abnormal bleeding. Campath destroys specific parts of the abnormal LGLs, which interfere with the production of normal blood cells. This study will determine whether Campath can increase blood counts and reduce the number of abnormal LGLs in patients and will examine the side effects of the drug. Patients 18 to 85 years of age with T-LGL leukemia may be eligible for this study. Participants undergo the following procedures: Before starting Campath treatment

• Medical history and physical examination, blood tests, electrocardiogram (ECG).
• Echocardiogram (heart ultrasound) and 24-hour Holter monitoring (continuous ECG recording).
• Bone marrow biopsy: About a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone. The procedure is done using local anesthetic.
• Placement of central line, if needed: An intravenous line (tube) is placed into a major vein in the chest. It can stay in the body and be used for the entire treatment period. The line is used to give chemotherapy or other medications, including antibiotics and blood transfusions, and to collect blood samples. The line is usually placed under local anesthesia in the radiology department or the operating room.
• Apheresis: A catheter (plastic tube) is placed in a vein in each arm. Blood is drawn from one vein and run through a cell-separating machine, where the white blood cells are collected and saved. The remaining blood is transfused back to the patients through the vein in the other arm. During Campath treatment
• Campath therapy: After a small test dose, patients receive10 daily infusions of Campath, each of which lasts about 2 hours. The first few infusions are given at the NIH Clinical Center so that the patient can be monitored closely.
• Induction therapy: Aerosolized pentamadine, valacyclovir and other medicines are given to protect against or treat various infections that commonly affect patients with suppressed immune systems.
• Whole blood or platelet transfusions, if needed, and injections of growth factors, if needed.
• Blood tests and check of vital signs (temperature, pulse, blood pressure) every day during treatment. Echocardiogram and 24-hour Holter monitor after the last dose of Campath. Follow-up evaluations after Campath treatment ends
• Blood tests at home or at NIH (weekly for the first 3 months, then every other week until 6 months, then annually for 5 years
• Echocardiogram at NIH (at 3 months only)
• Bone marrow biopsy at NIH (at 6 and 12 months, then as clinically indicated)
• One repeat apheresis collection for laboratory studies.

Conditions

T-LGL Lymphoproliferative Disorders

Keywords

Neutropenia; Monoclonal Antibody Therapy; Anti-CD52; T-LGL Leukemia; LGL Leukemia; Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematological Response After Three Months of Alemtuzumab

  The primary endpoint was hematologic response at three months after treatment. A complete response (CR) was defined as normalization of all affected lineages, and a partial response (PR) was defined in neutropenic subjects as 100% increase in the ANC to \>500/µL, and in those with anemia, any increase in hemoglobin of 2 g/dL or more observed in at least two serial measurements 1 week apart and sustained for one month or more without exogenous growth factors support or transfusions.

  3 months

Secondary Outcomes (8)

• Number of Participants That Are Red Blood Cell and/or Platelet Transfusion-Independent

  3 months

• Participants Overall Survival After Alemtuzumab Infusion

  3 months

• Number of Participants That Experienced a Life-Threatening Toxicity

  12 months

• Number of Participants That Are Relapse-free Survival Following Campath Infusion.

  Month 12

• Number of Participants With Molecular Response to Campath

  Up to Month 12

Study Arms (1)

Alemtuzumab in patients with T cell large granular lymphocytic leukemia (T-LGL)

EXPERIMENTAL

Alemtuzumab (Campath) will be administered at 10 mg/dose IV for 10 days as an infusion over 2 hours.

Biological: Alemtuzumab (Campath)

Interventions

Alemtuzumab (Campath) BIOLOGICAL

Alemtuzumab (Campath) will be administered at 10 mg/dose IV for 10 days as an infusion over 2 hours.

Alemtuzumab in patients with T cell large granular lymphocytic leukemia (T-LGL)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical history supportive of the diagnosis of T-LGL leukemia (i.e. a history of cytopenias with peripheral blood morphologic evidence of LGLs)
• Immunophenotypic studies of peripheral blood showing an increased population of T-LGLs (suggested by staining with CD3+, CD8+ and CD16+ or CD57+) or gammadelta T cells
• Restricted or clonal rearrangement of the T-cell receptor by PCR AND one or more of the following:
• Severe neutropenia (less than 500 neutrophils/microliter); OR
• Severe thrombocytopenia (less than 20,000 platelets/microliter), or moderate thrombocytopenia (less than 50,000 platelets/microliter) with active bleeding; OR
• Symptomatic anemia with a hemoglobin less than 9 g/dL or red blood cell transfusion requirement of greater than 2 units/month for two months prior to initiation of Campath
• Ages 18-85 (both inclusive)

You may not qualify if:

• A reactive LGL lymphocytosis to a viral infection
• Serologic evidence of HIV infection
• Infection not adequately responding to appropriate therapy
• Previous immunosuppressive therapy with alemtuzumab
• History of carcinoma that is not considered cured (excluding non-melanoma skin carcinoma)
• Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the subject's ability to tolerate protocol therapy or that death within 7-10 days is likely
• Current pregnancy or unwilling to take oral contraceptives or refrain from pregnancy if of childbearing potential
• Not able to understand the investigational nature of the study or give informed consent.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• McKenna RW, Parkin J, Kersey JH, Gajl-Peczalska KJ, Peterson L, Brunning RD. Chronic lymphoproliferative disorder with unusual clinical, morphologic, ultrastructural and membrane surface marker characteristics. Am J Med. 1977 Apr;62(4):588-96. doi: 10.1016/0002-9343(77)90422-3.

  PMID: 192076 BACKGROUND

• Loughran TP Jr. Clonal diseases of large granular lymphocytes. Blood. 1993 Jul 1;82(1):1-14.

  PMID: 8324214 BACKGROUND

• Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood. 1997 Jan 1;89(1):256-60.

  PMID: 8978299 BACKGROUND

• Dumitriu B, Ito S, Feng X, Stephens N, Yunce M, Kajigaya S, Melenhorst JJ, Rios O, Scheinberg P, Chinian F, Keyvanfar K, Battiwalla M, Wu CO, Maric I, Xi L, Raffeld M, Muranski P, Townsley DM, Young NS, Barrett AJ, Scheinberg P. Alemtuzumab in T-cell large granular lymphocytic leukaemia: interim results from a single-arm, open-label, phase 2 study. Lancet Haematol. 2016 Jan;3(1):e22-9. doi: 10.1016/S2352-3026(15)00227-6. Epub 2015 Dec 17.

  PMID: 26765645 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neutropenia; Leukemia, Large Granular Lymphocytic; Leukemia

Interventions

Alemtuzumab

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Leukemia, T-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Stefan F Cordes, Principal Investigator, M.D., Ph.D.
• Organization: National Heart Lung and Blood Institute

stefan.cordes@nih.gov

+1 240 383 6460

Study Officials

• Stefan F Cordes, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2006
• First Posted: June 28, 2006
• Study Start: October 17, 2006
• Primary Completion: August 1, 2017
• Study Completion: October 27, 2020
• Last Updated: May 3, 2022
• Results First Posted: May 3, 2019

Record last verified: 2021-03

Locations

US (1)