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A Phase I/II Trial of CpG 7909, Rituximab Immunotherapy, and Y-90 Zevalin Radioimmunotherapy for Patients With Previously Treated CD20+ Non-Hodgkin Lymphoma


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

A Phase I/II Trial of CpG 7909, Rituximab Immunotherapy, and Y-90 Zevalin Radioimmunotherapy for Patients With Previously Treated CD20+ Non-Hodgkin Lymphoma


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of CpG 7909 when administered in combination with
rituximab and yttrium 90 ibritumomab in patients with CD20+ recurrent or refractory
non-Hodgkin's lymphoma. (Phase I [closed to accrual as of 10/29/07])

- Assess the toxicity of this regimen in these patients. (Phase I [closed to accrual as
of 10/29/07])

Secondary

- Determine the response rate (complete response [CR], CR unconfirmed, and partial
response [PR]) in patients treated with this regimen. (Phase I [closed to accrual as of
10/29/07])

- Compare the biodistribution of indium In 111 ibritumomab tiuxetan radioimmunoconjugate
scans before and after treatment with CpG 7909. (Phase I [closed to accrual as of
10/29/07])

- Determine the human antimouse antibody and/or human antichimeric antibody rate in
patients treated with this regimen. (Phase I [closed to accrual as of 10/29/07])

- Determine if CpG 7909, when given in combination with rituximab and yttrium Y 90
ibritumomab tiuxetan, can stimulate immune effector cells in the blood and tumor tissue
of these patients. (Phase I [closed to accrual as of 10/29/07])

- Assess the overall response rate (CR and PR) in patients with relapsed diffuse large B
cell lymphoma treated with this regimen. (Phase II)

- Assess the toxicity of this regimen in patients with relapsed diffuse large B cell
lymphoma. (Phase II)

- Assess the time to progression and duration of response in patients with relapsed
diffuse large B cell lymphoma. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of CpG 7909 followed by a
phase II study. (Phase I closed to accrual as of 10/29/07.)

- Phase I (patients with relapsed, refractory, or residual CD20+ non-Hodgkin lymphoma
[closed to accrual as of 10/29/07]): Patients receive rituximab IV on days 1, 8, and
15, CpG 7909 IV over 2 hours on days 6, 13, 20, and 27, and yttrium Y 90 ibritumomab
tiuxetan* IV over 10 minutes on day 15 in the absence of disease progression or
unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of CpG 7909 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. Twelve additional patients are treated at the MTD.

NOTE: *Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on days 1 and
8. Patients undergo whole-body gamma camera imaging, single-photon emission computed
tomography/CT scans, and blood sampling after each dose of indium In 111 ibritumomab
tiuxetan to determine biodistribution. If biodistribution is acceptable, patients receive
yttrium Y 90 ibritumomab tiuxetan.

- Phase II (patients with relapsed, refractory, or residual diffuse large B-cell
lymphoma): Patients receive CPG 7909 at the MTD as determined in phase I. Patients also
receive rituximab and yttrium Y 90 ibritumomab tiuxetan as in phase I.

NOTE: *Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 8.
Patients undergo whole-body gamma camera imaging and blood sampling after each dose of
indium In 111 ibritumomab tiuxetan to determine biodistribution.

Blood samples are collected at baseline and periodically during treatment and follow up.
Samples are evaluated for immunology correlates by flow cytometry and immunoenzyme
techniques and biomarkers.

After the completion of study treatment, patients are followed periodically for up to 5
years.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed non-Hodgkin's lymphoma, including the following subtypes:

- Small lymphocytic lymphoma*

- Lymphoplasmacytoid lymphoma*

- Grade 1, 2, or 3 follicular lymphoma*

- Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue*

- Nodal marginal zone B-cell lymphoma*

- Splenic marginal zone B-cell lymphoma*

- Mantle cell lymphoma*

- Diffuse large cell lymphoma

- Transformed lymphoma NOTE: *Closed to accrual as of 10/29/07

- Recurrent, refractory, or residual disease

- CD20-positive disease

- Bidimensionally measurable disease (≥ 1 lesion that has a single diameter of ≥ 2 cm)

- Must have < 25% bone marrow involvement of cellular marrow with lymphoma, as
determined by bilateral bone marrow aspirate and biopsy

- No marrow cellularity ≤ 15% (as determined on all bone marrow samples)

- No prior failed stem cell collection

- No CNS lymphoma

- No lymphoma related to HIV or AIDS

- No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy ≥ 3 months

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 150,000/mm³

- Lymphocyte count < 5,000/mm³ (only for patients with small lymphocytic lymphoma)

- Hemoglobin ≥ 8 g/dL

- Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times
ULN

- Creatinine ≤ 2 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No serious nonmalignant disease (e.g., active infection) or other condition that
would preclude study participation

- No other active primary malignancy

- No known human antimouse antibodies or human antichimeric antibodies

- No skin rash (e.g., Stevens-Johnson's syndrome or toxic epidermal necrolysis) after
receiving rituximab

- No pre-existing clinical autoimmune or antibody-mediated diseases*, including any of
the following:

- Systemic lupus erythematosus

- Rheumatoid arthritis

- Multiple sclerosis

- Sjögren's syndrome

- Autoimmune thrombocytopenia

- NOTE: *If no clinical symptoms, but only previously detected antibodies, then not
excluded.

PRIOR CONCURRENT THERAPY:

- More than 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF) (3 weeks for
pegfilgrastim)

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas
or mitomycin C)

- More than 4 weeks since prior major surgery, except for diagnostic surgery

- More than 6 weeks since prior rituximab

- No prior external-beam radiotherapy to > 25% of active bone marrow

- No prior myeloablative therapies with autologous or allogeneic bone marrow
transplantation or peripheral blood stem cell support

- No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan,
tositumomab, or iodine I 131 monoclonal antibody Lym-1

- No concurrent myelosuppressive chemotherapy

- No concurrent corticosteroid therapy, except prednisone (< 20 mg) for benign causes

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Toxicity

Safety Issue:

Yes

Principal Investigator

Thomas E. Witzig, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Food and Drug Administration

Study ID:

LS0382

NCT ID:

NCT00438880

Start Date:

October 2004

Completion Date:

Related Keywords:

  • Lymphoma
  • recurrent adult diffuse large cell lymphoma
  • Waldenström macroglobulinemia
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent small lymphocytic lymphoma
  • recurrent mantle cell lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • recurrent marginal zone lymphoma
  • splenic marginal zone lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin

Name

Location

Mayo Clinic Cancer CenterRochester, Minnesota  55905
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002