Oblimersen, Rituximab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00086944
First received: July 8, 2004
Last updated: January 23, 2013
Last verified: January 2013
  Purpose

This phase I/II trial is studying the side effects and best dose of oblimersen when given together with rituximab and combination chemotherapy and to see how well they work in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may increase the effectiveness of chemotherapy by making cancer cells more sensitive to the drugs


Condition Intervention Phase
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Biological: oblimersen sodium
Biological: rituximab
Drug: ifosfamide
Drug: carboplatin
Drug: etoposide
Biological: filgrastim
Biological: pegfilgrastim
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Toxicity graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Complete and partial response rate according to the International Workshop Criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of response [ Time Frame: From the time measurement criteria are met for CR/CRu/PR until the first date that PD is objectively documented, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From the first day of therapy to the date of death, assessed up to 3 years ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: From the first day of treatment until the date PD or death is first reported, assessed up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: May 2004
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (genase, combination chemotherapy)
See detailed description.
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
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: pegfilgrastim
Given SC
Other Names:
  • Filgrastim SD-01
  • GCSF-SD01
  • Neulasta
  • SD-01 sustained duration G-CSF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of oblimersen when given in combination with rituximab, ifosfamide, carboplatin, and etoposide in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma.

II. Determine the safety and toxicity of this regimen in these patients. III. Determine the complete and partial response rate in patients treated with this regimen.

SECONDARY OBJECTIVES:

I. Determine the duration of response, overall survival, and time to progression in patients treated with this regimen.

II. Determine the effect of this regimen on hematopoietic stem cell kinetics and yield from these patients.

OUTLINE: This is a multicenter, phase I, dose-escalation study of oblimersen followed by a phase II study.

Phase I: Patients receive GRICE comprising oblimersen IV continuously on days 1-5, rituximab IV, ifosfamide IV continuously over 24 hours, and carboplatin IV over 1 hour on day 4, and etoposide IV over 30 minutes once daily on days 4-6. Treatment repeats every 14 days for 3 courses. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 7 and continuing until blood counts recover OR one dose of pegfilgrastim SC on day 7 of courses 1 and 2. For course 3, all patients receive G-CSF SC twice daily beginning on day 7 and continuing until stem cell collection is complete. Patients with responding disease who are not eligible for autologous SCT may receive up to 8 total courses of GRICE or 2 additional courses beyond maximal response. Patients with responding disease to GRICE who are eligible for autologous SCT are removed from the study and undergo autologous SCT off study. Cohorts of 3-6 patients receive escalating doses of oblimersen until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients receive oblimersen at the MTD determined in phase I and rituximab, ifosfamide, carboplatin, and etoposide followed by G-CSF or pegfilgrastim as in phase I. In both phases, treatment continues in the absence of disease progression, unacceptable toxicity, or the patient becomes a candidate for autologous SCT. Patients are followed for survival.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma

    • Any 1 one of the following histological subtypes for phase I:

      • Grade 3 follicular center lymphoma
      • Diffuse large B-cell lymphoma
      • Transformed follicular lymphoma
      • Mantle cell lymphoma
      • Primary mediastinal B-cell lymphoma
    • Any 1 of the following histological subtypes for phase II:

      • Diffuse large B-cell lymphoma
      • Transformed follicular lymphoma
      • Primary mediastinal B-cell lymphoma
  • Measurable disease

    • At least 1 bidimensionally measurable lesion ≥ 10 mm in longest diameter by CT scan, MRI, x-ray, or clinical exam
  • Relapsed disease after 1, and only 1, prior anthracycline-based chemotherapy regimen
  • No known brain metastases
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 3 months
  • Absolute neutrophil count ≥ 1,000/mm^3*
  • Platelet count ≥ 100,000/mm^3*
  • Bilirubin normal**
  • AST and ALT ≤ 2.5 times upper limit of normal
  • PT and PTT normal
  • Creatinine normal
  • Creatinine clearance ≥ 60 mL/min
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to oblimersen or other study drugs
  • No currently active second malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix

    • Must have completed any prior therapy for a second malignancy and is considered to be at < 30% risk of relapse
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other concurrent uncontrolled illness
  • Prior rituximab allowed
  • No other concurrent immunotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy
  • At least 4 weeks since prior radiotherapy and recovered
  • No concurrent therapeutic radiotherapy
  • At least 4 weeks since prior surgery
  • No prior oblimersen or other antisense oligonucleotide therapy
  • No other concurrent anticancer agents or therapies
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  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: NCT00086944

Locations
United States, Illinois
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
Investigators
Principal Investigator: Sonali Smith University of Chicago Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00086944     History of Changes
Other Study ID Numbers: NCI-2012-02600, 12975A, N01CM62201, CDR0000371904
Study First Received: July 8, 2004
Last Updated: January 23, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 19, 2014