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T-LGL Lymphoproliferative DisordersPhase 2NCT00345345

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

A Phase 2 study testing Alemtuzumab (Campath) in people with T-LGL Lymphoproliferative Disorders, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
T-LGL Lymphoproliferative Disorders
What is being tested?
Alemtuzumab (Campath)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteUnited States
Study dates
17 Oct 2006to 27 Oct 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Treatment of T-Large Granular Lymphocyte (T-LGL) Lymphoproliferative Disorders With Alemtuzumab (Campath)

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:

Read more

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.
Read the detailed description

T Cell Large Granular Lymphocyte (T-LGL) lymphoproliferative disorders are a heterogeneous group of uncommon diseases which may involve a monoclonal or oligoclonal T cell population, which bear characteristic surface markers corresponding to activated cytotoxic (CD3+, CD8+) lymphocytes. They are often associated with quite severe neutropenia, anemia, and thrombocytopenia, which may be life-threatening. There is some evidence that the abnormal cytotoxic lymphocyte population may cause the cytopenias by suppressing hematopoiesis, although the mechanism is unclear. Immunosuppressive therapy has been shown to improve the cytopenias of T-LGL leukemia, however the long-term use of the commonly used agents often lead to significant toxicity in the older patients which are affected by this disease.

Alemtuzumab (Campath[R]) is currently approved as second line agent in patients with chronic lymphocytic leukemia (CLL) and has been used successfully in the treatment of certain autoimmune disorders. In the Hematology Branch, Campath is currently being investigated in two bone marrow failure syndromes: aplastic anemia and myelodysplasia. Cytopenia(s) is an important characteristic of patients with T-LGL leukemia, often being the indication for immunosuppressive therapy. Our preliminary experience with Campath indicates that it is well tolerated, among the elderly patients.

Therefore, we propose this pilot, Phase II, single agent, study which will evaluate the efficacy and safety of alemtuzumab (Campath[R]), an immunosuppressive drug, in subjects with T-LGL leukemia. Commercially available Alemtuzumab (Campath[R]) will be administered off label at 10 mg per day by intravenous infusion for 10 days total. Subjects who do not show a response to initial Campath or relapse may receive a second cycle of drug after the 3-month time point.

The primary end point of the study is the response rate at three months, defined as improvement in cytopenia(s). Secondary endpoints will include relapse-free survival, response at 6 months, life threatening toxicity, reduction in the number of abnormal T-LGL clone, response to second cycle of Campath, and overall survival.

Being tested
Alemtuzumab (Campath)
Keywords
Neutropenia, Monoclonal Antibody Therapy, Anti-CD52, T-LGL Leukemia, LGL Leukemia, Leukemia
Medical subject headings
Neutropenia, Leukemia, Large Granular Lymphocytic, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Alemtuzumab (Campath)Biological

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

Study groups in NCT00345345
Study groupRoleWhat they receive
Alemtuzumab in patients with T cell large granular lymphocytic leukemia (T-LGL)ExperimentalAlemtuzumab (Campath) will be administered at 10 mg/dose IV for 10 days as an infusion over 2 hours.
Receives: Biological: Alemtuzumab (Campath)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 months

Secondary outcomes (8)

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

    Number of participants that are red blood cell and/or platelet Transfusion-Independent following Alemtuzumab

    Measured: 3 months

  2. Participants Overall Survival After Alemtuzumab Infusion

    Participants overall survival after Alemtuzumab infusion for cell large granular lymphocytic leukemia (T-LGL) at month 3.

    Measured: 3 months

  3. Number of Participants That Experienced a Life-Threatening Toxicity

    Number of participants that experienced a Life-Threatening Toxicity (grade >/= 4) as defined by Common toxicity Criteria (CTC) version 2.0. The CTC 2.0 is a set of criteria for the standardized classification of adverse effects. Adverse events are graded accordingly: 0 = No adverse event or within normal limits 1 = Mild adverse event 2 = Moderate adverse event 3 = Severe and undesirable adverse event 4 = Life-threatening or disabling adverse event 5 = Death related to adverse event

    Measured: 12 months

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

    Number of participants that are Relapse-free survival following Campath infusion. Relapse is defined as a fall in peripheral blood counts to 50% the values obtained during the response period.

    Measured: Month 12

  5. Number of Participants With Molecular Response to Campath

    Number of Participants with Molecular Response to Campath. Molecular Response to Campath is defined as disappearance of the clonal population of T-LGL

    Measured: Up to Month 12

  6. Participant Response at 6 Months

    Participant response at 6 months following Alemtuzumab. 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.

    Measured: 6 months

  7. Participants Response to a Second Cycle of Campath

    Participants Response to a second cycle of Campath. 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.

    Measured: 12 months

  8. Number of Participants With Clone Size Improvements

    Number of participants with clone size improvements following Alu

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jun 2006 (estimated)
  2. Study start17 Oct 2006
  3. Primary completion1 Aug 2017
  4. Study completion27 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00345345
Sponsor's protocol ID
060190
Other IDs
06-H-0190
Status last verified
Mar 2021
First submitted
27 Jun 2006
Last updated
3 May 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 192076

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

    PubMed 8324214

  • 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.

    PubMed 8978299

  • 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.

    PubMed 26765645

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alemtuzumab (Campath) in people with T-LGL Lymphoproliferative Disorders, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Hematological Response After Three Months of Alemtuzumab (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00345345, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2022.

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