Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI UCCRC-12975A 6243, NCI-6243, NCT00086944

Objectives

Primary

1. 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.
2. Determine the safety and toxicity of this regimen in these patients.
3. Determine the complete and partial response rate in patients treated with this regimen.

Secondary

1. Determine the duration of response, overall survival, and time to progression in patients treated with this regimen.
2. Determine the effect of this regimen on hematopoietic stem cell kinetics and yield from these patients.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• Prior rituximab allowed
• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• No concurrent hormonal therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy and recovered
• No concurrent therapeutic radiotherapy

Surgery

• At least 4 weeks since prior surgery

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3*
• Platelet count ≥ 100,000/mm^3*

 [Note: *Patients with absolute neutrophil count between 500/mm³- 1,000/mm³ and/or platelet count between 50,000mm³-100,000/mm³ due to non-Hodgkin's lymphoma are allowed at the discretion of the principal investigator]

Hepatic

• Bilirubin normal**
• AST and ALT ≤ 2.5 times upper limit of normal
• PT and PTT normal

 [Note: **Patients with known Gilbert's syndrome are allowed to participate in the phase II portion of the study]

Renal

• Creatinine normal

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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

Expected Enrollment

A total of 3-25 patients will be accrued for the phase I portion of this study. A total of 12-28 patients will be accrued for the phase II portion of this study. Patients will be accrued within 18 months.

Outcomes

Safety and tolerability
Toxicity
Maximum tolerated dose
Complete and partial response rate

Duration of response, overall survival, and time to progression
Pharmacodynamics
Effect on stem cell kinetics and yield

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.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Sonali Smith, MD, Protocol chair		Ph: 773-834-2895; 888-824-0200

Registry Information
Official Title		A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma
Trial Start Date		2004-05-19
Trial Completion Date		2006-07-10
Registered in ClinicalTrials.gov		NCT00086944
Date Submitted to PDQ		2004-05-18
Information Last Verified		2005-08-24
NCI Grant/Contract Number		CM17102, CA14599