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


Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

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


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.

Inclusion 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

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)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

Yes

Principal Investigator

John E. Janik, MD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Metabolism Branch;MET

Authority:

United States: Food and Drug Administration

Study ID:

020284

NCT ID:

NCT00047164

Start Date:

September 2002

Completion Date:

November 2010

Related Keywords:

  • Lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • recurrent adult lymphoblastic lymphoma
  • stage I adult lymphoblastic lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • stage I grade 3 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • contiguous stage II grade 3 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • stage I adult diffuse mixed cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • stage I adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • contiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • stage I adult immunoblastic large cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • contiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • recurrent adult Burkitt lymphoma
  • stage I adult Burkitt lymphoma
  • stage III adult Burkitt lymphoma
  • stage IV adult Burkitt lymphoma
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • stage I mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent adult Hodgkin lymphoma
  • stage I adult Hodgkin lymphoma
  • stage II adult Hodgkin lymphoma
  • stage III adult Hodgkin lymphoma
  • stage IV adult Hodgkin lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage II adult diffuse small cleaved cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • contiguous stage II marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • recurrent marginal zone lymphoma
  • splenic marginal zone lymphoma
  • stage I marginal zone lymphoma
  • stage III marginal zone lymphoma
  • stage IV marginal zone lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • recurrent small lymphocytic lymphoma
  • stage I small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage IV small lymphocytic lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • stage I adult T-cell leukemia/lymphoma
  • stage I cutaneous T-cell non-Hodgkin lymphoma
  • stage II adult T-cell leukemia/lymphoma
  • stage II cutaneous T-cell non-Hodgkin lymphoma
  • stage III adult T-cell leukemia/lymphoma
  • stage III cutaneous T-cell non-Hodgkin lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182