RFT5-dgA Immunotoxin in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

Phase II Study of IMTOX25 in Relapsed/Refractory Cutaneous T-Cell Lymphoma

RATIONALE: Immunotoxins, such as RFT5-dgA immunotoxin (also called anti-CD25 immunotoxin IMTOX25), can find certain cancer cells and kill them without harming normal cells.

PURPOSE: This phase II trial is studying the side effects of anti-CD25 immunotoxin IMTOX25 and how well it works in treating patients with relapsed or refractory cutaneous T-cell non-Hodgkin lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Other: immunohistochemistry staining method; Biological: RFT5-dgA immunotoxin; Other: fluorescence activated cell sorting

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate of patients with relapsed or refractory cutaneous T-cell non-Hodgkin lymphoma (CTCL) following treatment with RFT5-dgA immunotoxin (anti-CD25 immunotoxin IMTOX25) .

Secondary

• Determine whether responses correlate with the level of CD25+ expression on the CTCL tumor cells.
• Determine whether changes in the pre-treatment and the post-treatment levels of CD4+CD25+ Treg cells correlate with responses.

OUTLINE: Patients receive anti-CD25 immunotoxin IMTOX25 IV over 4 hours on days 1, 3, and 5. Treatment repeats every 6 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Tissue and blood samples are collected at baseline, and during study for CD25+ expression by fluorescent-activated cell sorter analysis, immunohistochemistry.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL)

• Relapsed or refractory disease, meeting 1 of the following criteria:

  • Progression of disease following 2 prior chemotherapies
  • Failure to respond to the second prior chemotherapy
• Measurable disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• Serum creatinine < 1.5 times upper limit of normal (ULN)
• Serum AST/ALT < 2.5 times ULN
• Total bilirubin ≤ 2.0 mg/dL (< 3.0 mg/dL in patients with Gilbert syndrome)
• WBC count ≥ 3,000/mm³
• Platelet count ≥ 100,000/mm³
• Serum albumin > 2.5 g/dL
• LVEF ≥ 45% by 2-D ECHO or MUGA scan
• Human antimurine antibody < 1 μg/mL
• Patients with a history of electrocardiogram abnormalities, symptoms of cardiac ischemia, or arrhythmias must have a normal cardiac stress test (i.e., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test)
• Must be willing to undergo venipuncture and central line placement
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HBV surface antigen, HCV, or HIV antibody positivity
• No autoimmune disease or immunodeficiency (i.e., HIV)

• No history of uncontrolled concurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Ongoing or active cardiac disease (i.e., congestive heart failure, unstable angina pectoris, or cardiac arrhythmia)
  • Psychiatric illness and/or social situation that would preclude study compliance
• No other malignancies except treated basal cell or squamous cell carcinoma of the skin, or treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• More than 3 weeks since prior systemic therapy for CTCL
• More than 6 months since prior chronic steroid therapy or chronic anti-coagulation therapy
• No prior therapy with anti-CD25 immunotoxin IMTOX25 and/or Ontak
• No other concurrent cancer chemotherapy, experimental therapy, investigational agent, or immunomodulating agent (including steroids)

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: IMTOX25 at 2mg/m²/dose; Patients will receive IMTOX25 at 2mg/m²/dose, by IV administration, every other day for a total of 3 doses. A total of 6 cycles of treatment will be allowed. A cycle is equal to 6 weeks, with IMTOX25 infusion on Day 1, 3 and 5, followed by a 5 week rest period.	Other: immunohistochemistry staining method; Biological: RFT5-dgA immunotoxin; Other: fluorescence activated cell sorting

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate - Cutaneous T Cell Lymphoma (CTCL)	Response rate of patients with relapsed/refractory Cutaneous T Cell Lymphoma (CTCL) following treatment with IMTOX25.	Once a week for seven weeks

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Simrit Parmar, MD, Simmons Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2008
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 24, 2008
• First Posted (Estimate): April 25, 2008

Study Record Updates

• Last Update Posted (Actual): December 14, 2018
• Last Update Submitted That Met QC Criteria: November 21, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma; Lymphoma, T-Cell, Cutaneous; Physiological Effects of Drugs; Immunologic Factors; Immunotoxins
• Other Study ID Numbers: SCCC-02407; CDR0000594170 (Registry Identifier: PDQ (Physician Data Query)); SCCC-122007-014