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.

Study Overview

• Status: Completed
• Conditions: Paraneoplastic Syndromes
• Intervention / Treatment: Drug: Tacrolimus

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Rockefeller University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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 Names: FK506

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival of Patients With Paraneoplastic Disease Who Are Treated With Tacrolimus	Survival in patients with paraneoplastic disease who are treated with Tacrolimus, from time of tacrolimus treatment	through study completion, median 3 years of follow up

Secondary Outcome Measures

Outcome Measure	Time Frame
Cerebrospinal Fluid (CSF) Pleocytosis	White blood cell count in CSF was measured at two time points, pre- and post-treatment

Collaborators and Investigators

• Sponsor: Rockefeller University
• Investigators: Principal Investigator: Robert Darnell, MD, PhD, Rockefeller University

Publications and helpful links

General Publications

• Orange D, Frank M, Tian S, Dousmanis A, Marmur R, Buckley N, Parveen S, Graber JJ, Blachere 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: September 18, 2006
• First Submitted That Met QC Criteria: September 19, 2006
• First Posted (Estimated): September 20, 2006

Study Record Updates

• Last Update Posted (Actual): September 18, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: paraneoplastic syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Syndrome; Paraneoplastic Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: RDA-0572