Non-Hodgkin's Lymphoma
Conditions
Keywords
oxaliplatin, ESHAOX, refractory, relapsed, non-hodgkin's lymphoma
Brief summary
Oxaliplatin will be used instead of cisplatin in well-known salvage regimen of etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP). Clinical efficacy and toxicity of this ESHAOX salvage regimen will be evaluated in refractory or relapsed non-Hodgkin's lymphoma patients.
Detailed description
Patients with aggressive non-Hodgkin's lymphoma (NHL) are known to have a malignancy considered curable in many cases. However, diagnosis of refractory or relapsed disease is devastating and the treatment is difficult because regimens of chemotherapy used as salvage therapy are available only in limited numbers. ESHAP, consisting of etoposide, methylprednisolone, high-dose cytarabine and cisplatin, is one of commonly used salvage regimen, and showed its efficacy and feasibility. But it often requires discontinuation of the treatment due to its myelosuppression, neuropathy and renal toxicity, which can also impede further treatment. Oxaliplatin, a platinum coordination complex with an oxalato-ligand as the leaving group and a 1,2-diaminocyclohexane carrier, possesses higher cytotoxic potency on molar basis than cisplatin and carboplatin, and was reported to be active in patients with NHL as a single agent. In addition, the substitution of cisplatin by oxaliplatin in the DHAP regimen, another commonly used one in relapsed or refractory NHL, showed meaningful anti-tumor activity with favorable toxicity profile. Based on preclinical and clinical findings, we will conduct a multi-center phase II study of ESHAOX, which substitutes oxaliplatin with cisplatin in the ESHAP regimen, to evaluate the efficacy and toxicity profile in patients with recurrent or refractory NHL.
Interventions
DRUGOxaliplatin
Oxaliplatin, 130 mg per square meter, on day 1
Sponsors
Boryung Pharmaceutical Co., Ltd
Asan Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No
Inclusion criteria
* Previously histologically confirmed aggressive lymphomas, defined according to WHO classification (except Burkitt's lymphoma, lymphoblastic lymphoma) * Failure to achieve a complete remission with the initial induction chemotherapy, or recurrent disease * Performance status (ECOG) ≤3 * Age ≤ 75 * Treated with at least one CHOP or CHOP-derived doxorubicin containing regimen * At least one or more uni-dimensionally measurable lesion(s) defined as; ≥2 cm by conventional CT or ≥ 1 cm by spiral CT or skin lesion (photographs should be taken) or measurable lesion by physical examination * Adequate organ functions defined as; ANC \> 1,500/ul, platelet \> 75,000/ul, transaminases \< 3 X upper normal values; bilirubin \< 2 mg% * Written informed consent approved by Institutional Review Board
Exclusion criteria
* Any other malignancies within the past 5 years except skin basal cell ca or CIS of cervix * Serious co-morbid diseases * Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | up to 24 weeks | The Overall Response Rate was measured by the number of patients per the total treatment population who partially or completely responded to treatment. Response was evaluated according to the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Toxicity Grade by Patient | up to 24 weeks | graded by National Cancer Institute Common Toxicity Criteria of Adverse Event version 3.0 |
Countries
South Korea
Participant flow
Recruitment details
A total of 27 patients were enrolled between April and December 2006 from eight institutions in South Korea.
Pre-assignment details
Patients with symptomatic central nervous system involvement and pregnant or breastfeeding women were excluded. Patients with grade 2 or more peripheral neuropathy at the time of study entry were also excluded.
Participants by arm
| Arm | Count |
|---|---|
| ESHAOx The ESHAOx consisted of Etoposide (40 mg per square meter on days 1-4), Methylprednisolone (500 mg on days 1-5), Cytarabine (2 g per square meter on day 5), and Oxaliplatin (130 mg per square meter on day 1) every 3 weeks to a maximum of six cycles. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | ESHAOx |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 55.2 years STANDARD_DEVIATION 10.8 |
| Region of Enrollment Korea, Republic of | 27 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 26 |
| serious Total, serious adverse events | 1 / 26 |
Outcome results
Primary
Overall Response Rate
The Overall Response Rate was measured by the number of patients per the total treatment population who partially or completely responded to treatment. Response was evaluated according to the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas.
Time frame: up to 24 weeks
Population: 25 patients who had completed at least 3 cycles of ESHAOx study treatment were analyzed. 2 patients who did not complete 3 cycles of study treatment were excluded from the response analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ESHAOx | Overall Response Rate | 17 pariticipants |
Secondary
Worst Toxicity Grade by Patient
graded by National Cancer Institute Common Toxicity Criteria of Adverse Event version 3.0
Time frame: up to 24 weeks
Population: The 27 patients received a total of 103 cycles of the ESHAOx treatment, with a median number of four cycles per patient. Except one who was lost to follow-up after one cycle, 26 patients were assessable for toxicity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ESHAOx | Worst Toxicity Grade by Patient | Grade 1 neutropenia | 3 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 2 neutropenia | 3 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 3 neutropenia | 2 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 4 neutropenia | 13 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 1 thrombocytopenia | 4 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 2 thrombocytopenia | 3 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 3 thrombocytopenia | 3 participants |
| ESHAOx | Worst Toxicity Grade by Patient | Grade 4 thrombocytopenia | 6 participants |