Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Monoclonal Antibody Therapy in Treating Patients With Lymphoma or Colon Cancer That Has Not Responded to Vaccine Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	NCI	NCI-02-C-0284 NCI-5744, NCT00047164, 5744

Special Category: NIH Clinical Center trial

Objectives

Primary

1. Determine the toxicity of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody in patients with follicular or mantle cell lymphoma, colon cancer, or prostate cancer refractory to vaccine therapy. (part I) (prostate cancer and mantle cell lymphoma closed to accrual as of 3/10/2005; colon cancer closed to accrual as of 9/28/05)
2. Determine the toxicity of this drug at escalating doses in patients with follicular lymphoma. (part II)
3. Determine the toxicity of this drug at escalating doses in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma. (part III)

Secondary

1. Determine the ability of this drug to increase tumor-specific T-cell responses in these patients.
2. Determine the ability of this drug to produce clinical tumor response in these patients.
3. Determine the effect of this drug on suppressor T-cell populations (CD4+ and CD25+ cells) in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed prostate cancer (closed to accrual as of 3/9/2005)
  • Prior therapy on protocol NCI-00-C-0137 or NCI-00-C-0154
  • Progressive disease (2 consecutively rising PSA levels, new bone scan lesion, or progression of soft tissue)
  • PSA at least 5 ng/mL
  • Progressive androgen-independent disease
    • Disease progression at least 4 weeks after flutamide withdrawal

      OR

    • Disease progression at least 6 weeks after bicalutamide or nilutamide withdrawal

  OR




• Histologically confirmed follicular or mantle cell non-Hodgkin's lymphoma (mantle cell lymphoma closed to accrual as of 3/9/2005)
  • Prior therapy on protocol NCI-00-C-0133, NCI-01-C-0169, or NCI-00-C-0050
  • Progressive disease after standard treatment
  • Relapsed disease

  OR




• Histologically confirmed colon cancer (colon cancer closed to accrual as of 9/28/05)
  • Prior therapy on protocol NCI-99-C-0023
  • Progressive disease

  OR




• Histologically confirmed non-Hodgkin's lymphoma or Hodgkin's lymphoma
  • Progressive disease after standard treatment
  • No curative therapy exists
  • Prior allogeneic stem cell transplantation from a matched sibling or matched unrelated donor for an aggressive lymphoma allowed
    • Last infusion of allogeneic cells (either hematopoietic stem cells or donor lymphocytes) must have occurred > 90 days prior to study enrollment



• No other standard therapy available or refused such therapy



• No symptomatic or rapidly progressive malignancy requiring therapy



• No symptomatic CNS metastases

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• Recovered from prior vaccine therapy
• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) for patients in part I of study
  • Patients in part II of study may have had up to 4 prior treatments with MDX-CTLA4
• No concurrent vaccine therapy
• No concurrent infliximab

Chemotherapy

• At least 4 weeks since prior cytotoxic chemotherapy
• No concurrent mercaptopurine, methotrexate, or cyclophosphamide

Endocrine therapy

• See Disease Characteristics
• At least 4 weeks since prior steroids
• No concurrent systemic, inhaled, or topical steroids

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• At least 4 weeks since prior major surgery

Other

• Prior intervening therapy for prostate cancer, non-Hodgkin's lymphoma or colon cancer allowed
• No other concurrent investigational therapy
• No other concurrent immunosuppressants (e.g., cyclosporine or its analog)

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• More than 2 months

Hematopoietic

• WBC at least 2,500/mm³
• Granulocyte count at least 1,500/mm³
• Platelet count at least 50,000/mm³
• Hemoglobin at least 10 g/dL
• Hematocrit at least 30%

Hepatic

• Bilirubin no greater than 3.0 mg/dL (unless due to Gilbert's disease)
• SGOT and SGPT no greater than 3 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine no greater than 2.0 mg/dL

Immunologic

• HIV negative
• Rheumatoid factor negative if history or evidence of arthritis
• Anti-nuclear antibody (ANA) titer no greater than 1:80 if history or clinical signs or symptoms of connective tissue disease
• No prior or active autoimmune disease (e.g., uveitis, rheumatoid arthritis, lupus erythematosus, autoimmune hemolytic anemia, ulcerative and hemorrhagic colitis, endocrine disorders [e.g., thyroiditis, hyperthyroidism, hypothyroidism, autoimmune hypophysitis/hypopituitarism, or adrenal insufficiency], sarcoid granuloma, myasthenia gravis, polymyositis,or Guillain-Barre syndrome)
• No positive antibody titers to autoimmune diseases
  • Rheumatoid factor positive allowed unless ANA titer is greater than 1:80 and there is a history of or clinical signs or symptoms of connective tissue disease
• No active infection

Other

• No other active malignancy within the past 5 years except adequately treated squamous cell or basal cell skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after study participation

Expected Enrollment

A total of 89 patients will be accrued for this study.

Outcomes

Toxicity after every 3 courses of treatment and every month for up to a year after completion of study treatment

T-cell response after every 3 courses of treatment and every month for up to a year after completion of study treatment

Outline

This is a pilot, partial dose-escalation study.

• Part I (patients with prostate or colon cancer or follicular or mantle cell lymphomas) (prostate cancer and mantle cell lymphoma closed to accrual as of 3/10/2005; colon cancer closed to accrual as of 9/28/05): Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4) IV over 90 minutes on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.



• Part II (dose-escalation) (patients with follicular lymphomas only): Patients receive MDX-CTLA4 as in part I. 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-CTLA4 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.




• Part III (dose-escalation*) (patients with non-Hodgkin's or Hodgkin's lymphoma): Patients receive MDX-CTLA4 as in part II.

   [Note: No dose-escalation for lymphoma patients who have previously been treated with an allogeneic stem cell transplantation.]

Patients are followed every other month.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

John Janik, MD, Protocol chair		Ph: 301-402-2913 Email: janikj@mail.nih.gov

U.S.A.
Maryland
	Bethesda
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Patient Recruitment	Ph:  888-NCI-1937

Related Information

PDQ® clinical trial NCI-00-C-0154
PDQ® clinical trial NCI-00-C-0137
PDQ® clinical trial NCI-00-C-0133
PDQ® clinical trial BIOVEST-BV301
PDQ® clinical trial NCI-99-C-0023L

Registry Information
Official Title		A Pilot Study of Ipilimumab (MDX-CTLA4, MDX-010) in Lymphoma
Trial Start Date		2002-09-02
Trial Completion Date		2009-10-01 (estimated)
Registered in ClinicalTrials.gov		NCT00047164
Date Submitted to PDQ		2002-08-15
Information Last Verified		2009-07-05

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