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

Lymphoma Clinical Trial

Official title:

A Pilot Study of Ipilimumab (MDX-CTLA4, MDX-010) in Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047164
• Other study ID #: 020284
• Secondary ID: 02-C-0284NCI-574
• Status: Completed
• Phase: Phase 1
• First received: October 3, 2002
• Last updated: September 23, 2016
• Start date: September 2002
• Est. completion date: November 2010

Study information

• Verified date: March 2012
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies such as anti-cytotoxic T-lymphocyte-associated antigen-4 can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells.

PURPOSE: This phase II trial is studying anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody to see how well it works in treating patients with lymphoma or colon cancer that has not responded to vaccine therapy.

Description:

OBJECTIVES:

Primary

• 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)

• Determine the toxicity of this drug at escalating doses in patients with follicular lymphoma. (part II)

• Determine the toxicity of this drug at escalating doses in patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma. (part III)

Secondary

• Determine the ability of this drug to increase tumor-specific T-cell responses in these patients.

• Determine the ability of this drug to produce clinical tumor response in these patients.

• Determine the effect of this drug on suppressor T-cell populations (CD4+ and CD25+ cells) in these patients.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: November 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• More than 2 months

Hematopoietic

• WBC at least 2,500/mm^3

• Granulocyte count at least 1,500/mm^3

• Platelet count at least 50,000/mm^3

• 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

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)

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• ipilimumab

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institutes of Health Clinical Center (CC)	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity after every 3 courses of treatment and every month for up to a year after completion of study treatment			Yes
Secondary	T-cell response after every 3 courses of treatment and every month for up to a year after completion of study treatment			No