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

Sponsors and Collaborators:	University of Chicago National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00086944

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Lymphoma	Drug: carboplatin Drug: etoposide Drug: filgrastim Drug: ifosfamide Drug: oblimersen Drug: pegfilgrastim Drug: rituximab	Phase I Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Ifosfamide Carboplatin Filgrastim Etoposide Rituximab Etoposide phosphate Pegfilgrastim Oblimersen sodium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma

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

Primary Outcome Measures:

Safety and tolerability [ Designated as safety issue: Yes ]
Toxicity [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]
Complete and partial response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of response, overall survival, and time to progression [ Designated as safety issue: No ]
Pharmacodynamics [ Designated as safety issue: No ]
Effect on stem cell kinetics and yield [ Designated as safety issue: No ]

Study Start Date:	May 2004
Primary Completion Date:	July 2006 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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

PROJECTED ACCRUAL: 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.

Eligibility

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

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086944

Locations

United States, Illinois
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 62701
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Ingalls Cancer Care Center at Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
La Grange Memorial Hospital
La Grange, Illinois, United States, 60525
Louis A. Weiss Memorial Hospital
Chicago, Illinois, United States, 60640
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
United States, Indiana
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46885-5099
United States, Michigan
Oncology Care Associates, PLLC
Saint Joseph, Michigan, United States, 49085

Sponsors and Collaborators

University of Chicago

National Cancer Institute (NCI)

Investigators

Study Chair:

Sonali M. Smith, MD

University of Chicago

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000371904, UCCRC-12975A, NCI-6243
Study First Received:	July 8, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00086944
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma
recurrent mantle cell lymphoma
recurrent grade 3 follicular lymphoma

Study placed in the following topic categories:

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Carboplatin
Etoposide phosphate
Mantle cell lymphoma
Recurrence
Lymphoma, large-cell

Lymphoma, B-Cell
Lymphatic Diseases
Ifosfamide
B-cell lymphomas
Lymphoma, Non-Hodgkin
Aggression
Lymphoproliferative Disorders
Etoposide
Lymphoma
Follicular lymphoma
Isophosphamide mustard

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents

Therapeutic Uses
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009