Bortezomib With Combination of Gemcitabine, Ifosfamide and Oxaliplatin in Untreated NK/T Cell Lymphoma (Gifox-B)

Phase II Trial of Bortezomib With Combination of Gemcitabine, Ifosfamide and Oxaliplatin (GIFOX-B)in Untreated NK/T Cell Lymphoma

• Assess responses, progression free survival (PFS) and overall survival (OS) of the combination of GIFOX-B chemotherapy with intensity-modulated radiation therapy (IMRT) in Stage IB or bulky disease - II and without IMRT in Stage III - IV.
• Assess the toxicity and maximum tolerated dose of bortezomib administered in combination with GIFOX chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Extranodal NK-T-CELL LYMPHOMA
• Intervention / Treatment: Drug: GIFOX-Bortezomib; Drug: GIFOX-Bortezomib; Radiation: IMRT

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Extranodal NK/T-cell lymphomas
2. Confirmed pathological diagnosis by the Department of Pathology SGH/NUH/TTSH.
3. Age more than or equals to 21 years.
4. Stages IB or bulky disease, II - IV
5. ECOG performance 0-2
6. Laboratory tests: ANC more than or equals to 1000/mm3, platelet more than or equals to 75,000/mm3. Creatinine less than or equals to 2x ULN or creatinine clearance more than or equals to 50 ml/min; AST and ALT less than or equals to 3x ULN. Total bilirubin < 1.5x ULN except < 3x ULN in patients with Gilbert's (as defined as > 80% unconjugated hyperbilirubinemia without other known cause); unless impairment is due to organ involvement by lymphoma.
7. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

1. Had prior systemic chemotherapy. Patients may be entered if they have had prior limited-field radiotherapy or a short course of glucocorticoids or single agent chemotherapy for an urgent local problem at diagnosis (e.g. epidural cord compression, superior vena caval syndrome).
2. History of peripheral neuropathy
3. HIV positive
4. Presence of CNS disease
5. Hypersensitivity to bortezomib, boron, or mannitol
6. Contraindication to any cytotoxic drug contained in the chemotherapy regimen.
7. Female subject of child-bearing potential not willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and one year beyond treatment completion.
8. Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum β-human chorionic gonadotrophin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without child-bearing potential.
9. Invasive or active malignancy in past 2 years.
10. Serious concomitant medical illnesses that would jeopardize the patient's ability to receive the regimen with reasonable safety.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early stage (IB or bulky disease - II); who will receive GIFOX-B chemotherapy followed by involved field radiotherapy.	Drug: GIFOX-Bortezomib; GIFOX-Bortezomib will be given every 21 days for 4 cycles; Drug: GIFOX-Bortezomib; GIFOX-Bortezomib will be given every 21 days for a total of 6 cycles.; Radiation: IMRT; a minimum of 50 Gy of IMRT to tumor bed and neck (5 weeks); Other Names: Intensity-modulated radiation therapy
Experimental: Advanced stage (III - IV); will receive only chemotherapy alone	Drug: GIFOX-Bortezomib; GIFOX-Bortezomib will be given every 21 days for 4 cycles; Drug: GIFOX-Bortezomib; GIFOX-Bortezomib will be given every 21 days for a total of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rates of bortezomib in combination with GIFOX (GIFOX-B) chemotherapy with or without intensity-modulated radiation therapy (IMRT)	Assess the response rates of bortezomib in combination with GIFOX (GIFOX-B) chemotherapy together with intensity-modulated radiation therapy (IMRT) in stage IB or bulky disease - II patients and chemotherapy alone in stage III - IV patients.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) of the combination of GIFOX-B chemotherapy with IMRT in stage IB and III - IV patients		3 years
Overall survival (OS) of the combination of GIFOX-B chemotherapy with IMRT in stage IB and III - IV patients		5 years
Toxicity of bortezomib administered in combination with GIFOX chemotherapy	Access the toxicity of treatment according to CTC AE 4.0	3 years

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Investigators: Principal Investigator: Soon Thye LIM, National Cancer Centre, Singapore

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: June 9, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimate): June 21, 2016

Study Record Updates

• Last Update Posted (Estimate): September 5, 2016
• Last Update Submitted That Met QC Criteria: September 2, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCC1004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No