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

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ClinicalTrials.gov Identifier: NCT00086944
Recruitment Status : Completed
First Posted : July 12, 2004
Last Update Posted : January 24, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 8, 2004
First Posted Date  ICMJE July 12, 2004
Last Update Posted Date January 24, 2013
Study Start Date  ICMJE May 2004
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • Toxicity graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ]
  • Complete and partial response rate according to the International Workshop Criteria [ Time Frame: Up to 3 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00086944 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2013)
  • 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 ]
  • Overall survival [ Time Frame: From the first day of therapy to the date of death, assessed up to 3 years ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Oblimersen, Rituximab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma
Official Title  ICMJE A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma
Brief Summary 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Treatment (genase, combination chemotherapy)
See detailed description.
Interventions:
  • Biological: oblimersen sodium
  • Biological: rituximab
  • Drug: ifosfamide
  • Drug: carboplatin
  • Drug: etoposide
  • Biological: filgrastim
  • Biological: pegfilgrastim
  • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 23, 2013)
25
Original Enrollment  ICMJE Not Provided
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date July 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00086944
Other Study ID Numbers  ICMJE NCI-2012-02600
12975A
N01CM62201 ( U.S. NIH Grant/Contract )
CDR0000371904 ( Registry Identifier: PDQ (Physician data Query) )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Sonali Smith University of Chicago Comprehensive Cancer Center
PRS Account National Cancer Institute (NCI)
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP