A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma

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Trial Information

A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma


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.


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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity graded using the NCI CTCAE version 3.0

Outcome Time Frame:

Up to 3 years

Safety Issue:

Yes

Principal Investigator

Sonali Smith

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02600

NCT ID:

NCT00086944

Start Date:

May 2004

Completion Date:

Related Keywords:

  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Mantle-Cell

Name

Location
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470