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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00829205
First received: January 23, 2009
Last updated: August 23, 2013
Last verified: July 2009
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
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:


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 ]

Enrollment: 0
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United Kingdom
Barts and the London NHS Trust
London, England, United Kingdom, EC1A 7BE
Saint Bartholomew's Hospital
London, England, United Kingdom, EC1A 7BE
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Derriford Hospital
Plymouth, England, United Kingdom, PL6 8DH
Southampton General Hospital
Southampton, England, United Kingdom, SO16 6YD
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Silvia Montoto, MD Barts and the London NHS Trust
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00829205     History of Changes
Other Study ID Numbers: CDR0000632722, CRUK-UCL-SelRICE, EUDRACT-2008-002678-36, EU-20902
Study First Received: January 23, 2009
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent adult diffuse large cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Etoposide phosphate
Isophosphamide mustard
Selenomethylselenocysteine
Carboplatin
Etoposide
Ifosfamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 18, 2014