Se-Methyl-Seleno-L-Cysteine, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Diffuse Large B-Cell Lymphoma That Has Relapsed or Not Responded to Treatment - Full Text View

Sponsored by:	Cancer Research UK
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00829205

Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer cell-killing substances to them. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Se-methyl-seleno-l-cysteine may help reduce the side effects of chemotherapy.

PURPOSE: This phase I/II trial is studying the side effects and best dose of Se-methyl-seleno-l-cysteine when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well it works in treating patients with diffuse large B-cell lymphoma that has relapsed or not responded to treatment.

Condition	Intervention	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Dietary Supplement: Se-methyl-seleno-L-cysteine Drug: carboplatin Drug: etoposide Drug: ifosfamide Other: laboratory biomarker analysis Other: pharmacological study	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	A Phase I/II Study of Methylselenocysteine (MSC) in Combination With Immunochemotherapy (R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Cysteine Etoposide Carboplatin Etoposide phosphate Filgrastim Rituximab Ifosfamide Cysteine hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

Dose-limiting toxicity and maximum tolerated dose of Se-methyl-seleno-L-cysteine (MSC) (Phase I) [ Designated as safety issue: Yes ]
Overall response rate (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity as assessed by NCI CTCAE v 3.0 [ Designated as safety issue: Yes ]
Serum and intracellular Se and Se species [ Designated as safety issue: No ]
Pharmacokinetics of MSC [ Designated as safety issue: No ]
Protein markers of selenium activity [ Designated as safety issue: No ]

Estimated Enrollment:	51
Study Start Date:	January 2009

Detailed Description:

OBJECTIVES:

Primary

To assess dose-limiting toxicity and maximum-tolerated dose (MTD) of Se-methyl-seleno-L-cysteine (MSC) (to achieve a trough serum selenium [Se] concentration of > 20 μmol/L) prior to and in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with relapsed or refractory diffuse large B-cell lymphoma. (Phase I)
To determine the overall response rate to R-ICE given in addition to MSC at the MTD in these patients. (Phase II)

Secondary

To determine the toxicity of R-ICE when used in combination with MSC in these patients.
To determine the effect of MSC dosing on serum and intracellular Se and Se species in these patients.
To determine the pharmacokinetics of MSC after single and multiple daily dosing in these patients.
To investigate the effect of MSC dosing on Se-dependent processes (e.g., NFκB activity and AKT).

OUTLINE: This is a multicenter, phase I, dose-escalation study of Se-methyl-seleno-L-cysteine (MSC) followed by a phase II study.

Patients receive rituximab IV on day 1, carboplatin IV on day 2, ifosfamide IV and etoposide IV on days 2-4 (R-ICE), and filgrastim (G-CSF) subcutaneously on days 6-13. Patients also receive oral MSC twice daily on days

7 to 0 and once daily in courses 1-2. Treatment with R-ICE and G-CSF repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically and analyzed for pharmacokinetics and protein markers.

After completion of study treatment, patients are followed monthly for 3 months.

This study is peer reviewed and funded or endorsed by cancer research UK.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed, CD20+, diffuse large B-cell lymphoma (DLBCL) according to WHO lymphoma classification
- Histological transformation of a previously known indolent lymphoma allowed
- Biopsy-proven DLBCL arising from an indolent lymphoma not diagnosed previously allowed
Disease in first relapse after complete remission, partial response (PR), or less than a PR after first-line of treatment
No primary CNS lymphoma

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 3 months
Serum creatinine < 150 μmol/L
Serum bilirubin < 35 μmol/L
Transaminases < 2.5 times upper limit of normal (unless attributed to lymphoma)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No contraindication to any of the drugs contained in the immunochemotherapy regimen
No other malignancy within the past 2 years, except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
No other serious active disease that, in the opinion of the investigator, would preclude the patient from having conventional chemotherapy
No HIV positivity
No medical or psychiatric conditions that compromise the patient's ability to give informed consent

PRIOR CONCURRENT THERAPY:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00829205

Locations

United Kingdom, England
Barts and the London NHS Trust	Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Silvia Montoto, MD 44-2076-017-456
Christie Hospital	Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: John Radford, MD 44-161-446-3753
Derriford Hospital	Recruiting
Plymouth, England, United Kingdom, PL6 8DH
Contact: Simon Rule, MD 44-1752-517-505
Saint Bartholomew's Hospital	Recruiting
London, England, United Kingdom, EC1A 7BE
Contact: Contact Person 44-20-7601-8391
Southampton General Hospital	Recruiting
Southampton, England, United Kingdom, SO16 6YD
Contact: Peter Johnson, MD 44-238-079-6185 johnsonp@soton.ac.uk

Sponsors and Collaborators

Cancer Research UK

Investigators

Principal Investigator:

Silvia Montoto, MD

Barts and the London NHS Trust

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000632722, CRUK-UCL-SelRICE, EUDRACT-2008-002678-36, EU-20902
Study First Received:	January 23, 2009
Last Updated:	July 28, 2009
ClinicalTrials.gov Identifier:	NCT00829205 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent adult diffuse large cell lymphoma

Study placed in the following topic categories:

Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Immunologic Factors
Rituximab
Carboplatin
Etoposide phosphate
Recurrence
Lymphoma, B-Cell
Lymphatic Diseases
Ifosfamide
B-cell Lymphomas
Cysteine

Mechlorethamine
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma, Large-cell
Alkylating Agents
Antineoplastic Agents, Phytogenic
Etoposide
Lymphoma
Isophosphamide mustard

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Lymphoma, B-Cell
Therapeutic Uses
Etoposide
Lymphoma
Alkylating Agents
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases

Rituximab
Carboplatin
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Ifosfamide
Antineoplastic Agents, Alkylating
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Isophosphamide mustard

ClinicalTrials.gov processed this record on September 10, 2009