Immunotherapy of the Paraneoplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00378326
Recruitment Status : Completed
First Posted : September 20, 2006
Results First Posted : February 23, 2016
Last Update Posted : February 23, 2016
Information provided by (Responsible Party):
Rockefeller University

September 18, 2006
September 20, 2006
November 2, 2015
February 23, 2016
February 23, 2016
April 2006
May 2014   (Final data collection date for primary outcome measure)
Survival of Patients With Paraneoplastic Disease Who Are Treated With Tacrolimus [ Time Frame: through study completion, median 3 years of follow up ]
Survival in patients with paraneoplastic disease who are treated with Tacrolimus, from time of tacrolimus treatment
  • Assessment of immune responses
  • Clinical response in PND patients who are treated with Tacrolimus and Prednisone
Complete list of historical versions of study NCT00378326 on Archive Site
Cerebrospinal Fluid (CSF) Pleocytosis [ Time Frame: White blood cell count in CSF was measured at two time points, pre- and post-treatment ]
Collection and archiving of serum and lymphocytes for future studies on the mechanism of neuronal autoimmunity.
Not Provided
Not Provided
Immunotherapy of the Paraneoplastic Syndromes
Immunotherapy of the Paraneoplastic Syndromes
We treat a subset of patients with paraneoplastic neurologic disorders, including those with Yo-mediated paraneoplastic cerebellar degeneration (PCD), the Hu syndrome, which is most commonly associated with small cell lung cancer (SCLC) - paraneoplastic subacute sensory neuropathy, encephalomyelitis, limbic encephalopathy, autonomic neuropathy - and the Ri Syndrome (a.k.a. Paraneoplastic Opsoclonus-Myoclonus Ataxia), as well as those patients suspected to have a paraneoplastic neurologic disorder but in whom a characteristic antibody has not yet been identified. Our treatment protocol consists of immune suppression therapy using tacrolimus (FK506), a potent inhibitor of lymphocyte proliferation that is commonly used to prevent organ transplant rejection.

Patients may stay either in-hospital while being treated with Tacrolimus, receive treatment as an outpatient, or a combination of the two. Additionally, patients who are too sick to be treated at Rockefeller University (RU) (eg. patients actively seizing), but are in need of urgent treatment, may be treated at either Memorial Sloan-Kettering Cancer Center or New York-Presbyterian Hospital. During treatment, patients will undergo blood draws, at set intervals (see section g below), clinical evaluation, possibly repeat leukapheresis or large volume blood draw, and lumbar puncture (see below). Since many patients live far away from New York, some of these procedures may be performed by RU staff or in conjunction with their local MDs.

Patients who are terminated from Tacrolimus treatment after 7-21 days will be followed up as outpatients for evaluation of their neurologic and medical status. Wherever possible, these patients will be seen on days 3 and 10 post treatment termination, and then on a biweekly basis for two months. Since many patients live far away from New York, they may instead be monitored in conjunction with their local MDs. Patients who show a definite clinical response to Tacrolimus may be maintained on a therapeutic dose for up to one year, and will be followed as outpatients. For patients receiving retreatment, they may be treated as inpatients or on an outpatient basis, at the discretion of the PI, on the same schedule as patients being treated initially. Long term improvement or decline in neurologic function will be objectively assessed by neurologic exam, which will be quantified by use of the Karnofsky scale (a measure of functional neurologic status). Since the vast majority of Hu patients decline over a 6-12 month period following diagnosis, a stable or improved Karnofsky score over such a time period will be taken as a measure of successful treatment. Repeat lumbar puncture (up to eight per year) and leukapheresis or large volume blood draw (approx. 100 cc) may be performed (up to four of each per year), especially in the setting of neurologic change, to assess the immune responses to the medications.

Not Applicable
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Paraneoplastic Syndromes
Drug: Tacrolimus
Tacrolimus at doses of 0.15- 0.3mg/kg/day in two divided oral doses, in conjunction with, initially, up to 60mg/day of oral prednisone
Other Name: FK506
Experimental: Tacrolimus
Tacrolimus at doses of 0.15- 0.3mg/kg/day in two divided oral doses, in conjunction with, initially, up to 60mg/day of oral prednisone
Intervention: Drug: Tacrolimus
Orange D, Frank M, Tian S, Dousmanis A, Marmur R, Buckley N, Parveen S, Graber JJ, Blachère N, Darnell RB. Cellular immune suppression in paraneoplastic neurologic syndromes targeting intracellular antigens. Arch Neurol. 2012 Sep;69(9):1132-40. doi: 10.1001/archneurol.2012.595.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
May 2014
May 2014   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients diagnosed with Paraneoplastic Disorder

Exclusion Criteria:

  • Metastasis (spread) of cancer to brain, History of additional active malignancy other than non-melanoma skin cancer, History of Hepatitis B, Hepatitis C, HIV or Syphilis.
Sexes Eligible for Study: All
14 Years and older   (Child, Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
Not Provided
Not Provided
Rockefeller University
Rockefeller University
Not Provided
Principal Investigator: Robert Darnell, MD, PhD Rockefeller University
Rockefeller University
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP