Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00301795
First received: March 9, 2006
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Oblimersen may help rituximab work better by making cancer cells more sensitive to the drug. This phase II trial is studying how well giving rituximab together with oblimersen works in treating patients with stage II, stage III, or stage IV follicular non-Hodgkin's lymphoma


Condition Intervention Phase
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Biological: oblimersen sodium
Biological: rituximab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Rituximab + Oblimersen Sodium (GenasenseTM, G3139, NSC #683428, IND #58842) in Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall response (OR) rate defined as achievement of a complete (CR) or partial response (PR) as the best observed response [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The true OR rate will be estimated using the uniformly minimum unbiased estimator. Jennison and Turnbull's method will be used to obtain 95% exact confidence interval for the true OR rate of each arm reflecting the above two-stage design.


Secondary Outcome Measures:
  • Toxicities assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    Will be summarized using frequency tables.

  • Time-to-progression (TTP) [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Time-to-best response [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.

  • Overall survival [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used.


Estimated Enrollment: 52
Study Start Date: March 2006
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (oblimersen sodium and rituximab)

Induction therapy (month 1): Patients receive oblimersen IV continuously on days 1-7 and 15-21 and rituximab IV on days 3, 10, 17, and 24 in month 1.

Extended induction therapy (months 3, 5, 7, and 9): Patients receive oblimersen IV continuously on days 22-28 and rituximab IV on day 24 in months 3, 5, 7, and 9.

Treatment continues for 9 months in the absence of disease progression or unacceptable toxicity.

Biological: oblimersen sodium
Given IV
Other Names:
  • augmerosen
  • G3139
  • G3139 bcl-2 antisense oligodeoxynucleotide
  • Genasense
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the response rate (overall and complete response rate) after rituximab + oblimersen sodium extended induction therapy in previously untreated cluster of differentiation 20 positive (CD20+) follicular non-Hodgkin lymphoma (NHL) patients.

II. To determine the time to progression after rituximab + oblimersen sodium extended induction therapy in previously untreated CD20+ follicular NHL patients.

SECONDARY OBJECTIVES:

I. To determine the toxicity profile of rituximab + oblimersen sodium therapy in previously untreated CD20+ follicular NHL patients.

II. To establish whether the therapeutic effects of the rituximab + oblimersen sodium combination are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).

III. To correlate Fc receptor profiling to response to rituximab + oblimersen sodium in previously untreated patients with follicular NHL.

IV. To determine the relationship between change in fludeoxyglucose F 18 (FDG) uptake early after treatment with rituximab + oblimersen sodium to response rate and time to progression.

OUTLINE: This is a multicenter study.

Induction therapy (month 1): Patients receive oblimersen IV continuously on days 1-7 and 15-21 and rituximab IV on days 3, 10, 17, and 24 in month 1.

Extended induction therapy (months 3, 5, 7, and 9): Patients receive oblimersen IV continuously on days 22-28 and rituximab IV on day 24 in months 3, 5, 7, and 9.

Treatment continues for 9 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 10 years.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Previously untreated, histologically confirmed follicular lymphoma, WHO classification, grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) which is stage III, IV, or bulky (i.e., single mass >= 7 cm in any unidimensional measurement) stage II
  • Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression
  • Patients classified as high risk according to the Follicular Lymphoma International Prognostic Index (FLIPI) should be considered for CALGB 50102/SWOG S0016
  • No prior therapy for non-Hodgkin lymphoma including chemotherapy, radiation or immunotherapy (e.g., monoclonal antibody-based therapy)
  • No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease
  • ECOG performance status 0-2
  • Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable; lesions that are considered non-measurable include the following:

    • Bone lesions (lesions if present should be noted)
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Bone marrow (involvement by non-Hodgkin lymphoma should be noted)
  • No known CNS involvement by lymphoma
  • No known HIV infection
  • Non-pregnant and non-nursing; women and men of reproductive potential should agree to use an effective means of birth control throughout their participation in this study; appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
  • Patients with a "currently active" second malignancy, other than nonmelanoma skin cancers are not eligible; (this includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis); patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse
  • ANC >= 1000/uL
  • Platelet count >= 50,000/uL
  • Creatinine =< 2 x ULN
  • Total bilirubin =< 2 x ULN; unless attributable to Gilbert's disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301795

Locations
United States, Illinois
Cancer and Leukemia Group B
Chicago, Illinois, United States, 60606
Sponsors and Collaborators
Investigators
Principal Investigator: Barbara Grant Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00301795     History of Changes
Other Study ID Numbers: NCI-2012-03080, CALGB 50404, U10CA031946, CDR0000462385
Study First Received: March 9, 2006
Last Updated: January 4, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 20, 2014