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Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma

Phase 2
18 Years
Not Enrolling
Metastatic Melanoma

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Trial Information

Phase II Evaluation of RFT5-dgA in Patients With Metastatic Melanoma


- RFT5-dgA is an immunotoxin comprised of the IL-2Ra-specific murine IgG1 antibody RFT5
linked to deglycosylated ricin A chain (dgA) via the sterically hindered
heterobifunctional disulfide linker SMPT

- RFT5-dgA is a recombinant immunotoxin that selectively targets CD25 expressing cells in
vivo. Further, treatment of human PBMC with RFT5-dgA in vitro results in the
preferential depletion of CD25+ Treg cells.

- Depletion of Treg cells can enhance tumor protection to tumor-associated antigens
expressed as self antigens and the RFT5-dgA immunotoxin had potent antitumor effects in
SCID mice xenografted with L540 cells which express CD25.

- The MTD established in the phase I trial of RFT5-dgA was 15mg/m(2)/course IV.


- The primary objective is to determine whether objective clinical responses can be
obtained in patients with metastatic melanoma following administration of RFT5-dgA.

- Secondary objectives will determine whether changes occur in levels of CD4+CD25+
regulatory T cells (Treg cells) in peripheral blood from before to after treatment and
evaluate the toxicity profile of patients treated on this trial.


- Patients greater than 18 years of age with measurable metastatic melanoma, an expected
survival greater than three months, who have progressed after receiving standard
therapy will be included.

- Standard clinical laboratory values must be normal for study inclusion and patients may
not be pregnant, breast-feeding or require anticoagulation.

- Patients must be willing to undergo leukapheresis.

- Patients with active infections, other major medical disorders, HAMA levels greater
than 1 ug/mL, or who have had prior radiotherapy or who have extensive lung disease
will be excluded.


- Patients will receive 3 mg/m(2) RFT5-dgA intravenously every other day for a total of 3
doses (one course).

- Four to five weeks after the last dose, patients will undergo tumor evaluation,
evaluation of changes in T-regulatory cells (CD4+CD25+cells and Foxp3 expression), and
toxicity assessment.

- One additional course may be administered to patients with stable disease or partial or
complete response.

- Up to 41 evaluable patients may be accrued to determine whether theRFT5-dgA can produce
a modest response rate targeted to be 20 percent (p1=0.20)

Inclusion Criteria


1. Patients age greater than 18 with measurable metastatic melanoma that have an
expected survival of greater than three months will be considered. Patients with
resectable local/regional disease would undergo standard treatment with surgical
resection and will not be eligible.

2. Patients must be able to understand and give informed consent.

3. Patients must have progressed while receiving standard therapy which may include
IL-2; however, prior IL-2 therapy is not a requirement for enrollment.

4. Serum creatinine of 1.6 mg/dl or less.

5. Total bilirubin 2.0 mg/dl or less, except for patients with Gilbert's Syndrome
who must have a total bilirubin less than 3.0 mg/dl.

6. WBC 3000/mm(3) or greater.

7. Platelet count 90,000 mm(3) or greater

8. Serum albumin greater than 2.5 g/dl,

9. Serum AST/ALT less then 2.5 times normal,

10. ECOG performance status of 0 or 1 or 2.

11. For patients greater than 50 years of age or who have a history of
cardiovascular disease a thallium stress test is required with EF greater than
or equal to 45%.

12. Patients of both genders must be willing to practice effective birth control
during this trial.

13. Patients must be willing to undergo leukapheresis.


Patients will be excluded:

1. who are undergoing or have undergone in the past 3 weeks any other systemic form of
therapy for their cancer.

2. who received RFT5-dgA on another trial.

3. who have uncontrolled concurrent illness including, but not limited to: ongoing or
active infection; ongoing or active cardiac disease, such as symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia; or psychiatric
illness/social situations that would limit compliance with study requirements.

4. who require systemic steroid therapy upon entry into the trial.

5. who are pregnant or breast-feeding.

6. who are known to be positive for hepatitis B(s)AG, hepatitis C or HIV antibody
(because of possible immune effects of these conditions).

7. who require chronic anticoagulation.

8. who are 50 years old or greater who do not have a normal stress cardiac test (stress
thallium, stress MUGA, dobutamine echocardiogram, or other stress test) with a LVEF
less than 45%.

9. who have history of EKG abnormalities, symptoms of cardiac ischemia or arrhythmias
who do not have a normal stress cardiac test (stress thallium, stress MUGA,
dobutamine echocardiogram, or other stress test) with a LVEF lea than 45%.

10. who have any autoimmune diseases or immunodeficiency (including HIV),or other
concurrent malignancies.

11. Who have HAMA levels greater than 1 ug/mL.

12. Who have had prior radiotherapy including radiotherapy to the lung, except for
patients who have undergone localized soft tissue radiotherapy.

13. Who have extensive lung disease where greater than 15% of the lung is involved based
on CT evaluation.

Type of Study:


Study Design:

Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

April 2006

Completion Date:

November 2008

Related Keywords:

  • Metastatic Melanoma
  • Clinical Response
  • Stage IV Melanoma
  • Immunotoxin
  • T Regulatory Cells
  • CD25+ Cells
  • Metastatic Melanoma
  • Melanoma



National Cancer Institute (NCI)Bethesda, Maryland  20892