Immunotherapy of the Paraneoplastic Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Rockefeller University
Sponsor:
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT00378326
First received: September 18, 2006
Last updated: May 5, 2014
Last verified: May 2014

September 18, 2006
May 5, 2014
April 2006
May 2015   (final data collection date for primary outcome measure)
  • Assessment of immune responses [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Clinical response in PND patients who are treated with Tacrolimus and Prednisone [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • 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 ClinicalTrials.gov Archive Site
Collection and archiving of serum and lymphocytes for future studies on the mechanism of neuronal autoimmunity. [ Time Frame: end of study ] [ Designated as safety issue: No ]
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. POMA - 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 (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 in conjunction with MDs there. Dr. Robert Darnell, being credentialed at both institutions, will be the primary person responsible for monitoring all portions of the study performed at MSKCC and 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 NY, 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 NY, 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 (see 10.g.). 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.

Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Paraneoplastic Syndromes
Drug: Tacrolimus (FK506)
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
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 (FK506)
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 1;69(9):1132-40. doi: 10.1001/archneurol.2012.595.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
May 2015
May 2015   (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.
Both
16 Years to 75 Years
No
Contact: Mayu Frank, NP 212-327-7443 frankm@rockefeller.edu
United States
 
NCT00378326
RDA-0572
Yes
Rockefeller University
Rockefeller University
Not Provided
Principal Investigator: Robert Darnell, MD, PhD Rockefeller University
Rockefeller University
May 2014

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