Clinical Trial for Lymphoma: 02-C-0284: 1.888.NCI.1937

A Pilot Study of MDX-CTLA-4 in Lymphoma

Protocol # 02-C-0284

Why is this trial important?
Who is eligible for this trial?
What types of drugs or therapies are being used?
What is the treatment plan?
What is the frequency and duration of the visits?
What are the costs?
Who is the Principal Investigator?
Where is this trial taking place?
Who are the contacts for this trial?
Where can additional information be found?

Why is this trial important?

Monoclonal antibodies have become an important addition to the management of patients with cancer. MDX-CTLA-4 is a human antibody that binds to a protein called CTLA-4. The antibody interrupts signals by CTLA-4 and may act to inhibit the normal pathways that regulate and control the expansion of T cells. Although this process has been associated with tumor responses in patients with lymphoma and other cancers, it is not clear why some people develop an autoimmune disorder while others do not. We are trying to find out if the development of autoimmunity has a direct relationship with tumor response and if there are features in tumors that predict a greater chance for response to treatment.

Who is eligible for this trial? (PDQ)

Histologically confirmed non-Hodgkin’s lymphoma or Hodgkin’s lymphoma
Progressive disease
No other standard therapy available or refused such therapy
No symptomatic or rapidly progressive malignancy requiring therapy
No symptomatic CNS metastases
Recovered from all prior therapy
No concurrent therapy allowed
Karnofsky 80–100%
WBC ≥ 2,500/mm³; granulocyte count ≥ 1,500/mm³; platelet count ≥ 50,000/mm³; hemoglobin ≥ 10 g/dL; hematocrit ≥ 30%
Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert’s disease); SGOT and SGPT ≤ 3 x upper limit of normal (ULN); hepatitis B surface antigen negative; hepatitis C antibody negative
Creatinine ≤ 2.0 mg/dL
No prior or active autoimmune disease
HIV negative
Not pregnant of nursing; fertile patients must use effective contraception during and for 4 months after study participation
No other medical conditions that would preclude study participation

What types of drugs or therapies are being used?

Patients are given a 90-minute IV infusion of a human antibody called MDX-CTLA-4. The doses vary depending on the type of cancer.

What is the treatment plan? (PDQ)

This is a pilot, partial dose-escalation study.

Part I

Part II

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA-4) IV over 90 minutes on Day 1
Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity
Cohorts of 3–6 patients receive escalating doses of MDX-CTLA-4 until the maximum tolerated dose (MTD) is determined; the MTD is defined as the dose preceding at which 2 of 6 patients experience dose-limiting toxicity

Part III

Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA-4) IV over 90 minutes on Day 1
Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity
Patients are followed every other month

What is the frequency and duration of the visits?

The drug is given once per cycle with 2 weeks of rest between treatments. Each cycle is 3 weeks in duration and patients can be given as many as 6 cycles of treatment. Depending on where the patient lives, the visits can be as short as 3 hours or as long as 2 days. The actual drug infusion is 90 minutes and vital signs are monitored for 1 hour after the infusion. Blood work is required once a week; this can be done through the patient’s local physician.

What are the costs?

There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.

It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.

No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.

Who is the Principal Investigator?

Dr. John E. Janik received his M.D. from the Ohio State University College of Medicine in 1977 and completed clinical training in internal medicine at Baylor College of Medicine Affiliated Hospitals and hematology/oncology training at Case Western Reserve University. He joined NCI in 1989 at the Biological Response Modifiers Program in Frederick, Md. In 1999, he was appointed the co-director, Clinical Trials Team, in the Metabolism Branch.

Where is this trial taking place?

NIH Clinical Center
National Institutes of Health
NCI Metabolism Branch
10 Center Drive
Bethesda, Maryland 20892

Who are the contacts for this trial?

John E. Janik, M.D.
Principal Investigator
Phone: 301-402-2913
janikj@mail.nih.gov

Referrals:

Guinevere Chun, R.N., B.S.N., O.C.N.
Research Nurse
Phone: 301-451-7868
Fax: 301-402-1001
gchun@mail.nih.gov

Suzanne Fioravanti, R.N., B.S.N., O.C.N.
Research Nurse
Phone: 301-594-6544
Fax: 301-402-1001
fioravas@mail.nih.gov