Lymphoma
Conditions
Keywords
Hodgkin Lymphoma, Non-Hodgkin's Lymphoma, Bone marrow transplant, stem cell transplant, busulfan, cyclophosphamide, etoposide
Brief summary
This is a study for the outcome and safety of individualized busulfan dosing with cyclophosphamide and etoposide for patients preparing for a stem cell transplant to treat Non-Hodgkin or Hodgkin's Lymphoma.
Detailed description
Evaluation of progression-free survival, transplant related mortality, overall survival, and overall response rate, in subjects with NHL and HL receiving an IV busulfan-based conditioning regimen with PK-guided IV busulfan dosing, followed by autologous HSCT as well as comparison to those receiving carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning regimen (and its variants) obtained from registry data in the Center for International Blood and Marrow Transplant Research (CIBMTR) Assessment of the safety profile of a BuCyE conditioning regimen with PK-directed dosing of IV busulfan will also be completed.
Interventions
DRUGIV Busulfan, Cyclophosphamide and Etoposide (BuCyE Regimen)
Pk-directed IV Busulfan (based on test dose method) for 4 days followed by Etoposide 1400mg/m2 QD for one day and Cyclophosphamide 2.5 g/m2 QD for two days followed by autologous stem cell transplant.
Sponsors
Center for International Blood and Marrow Transplant Research
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects with NHL to be included: * Any subject with NHL that had relapsed or progressed following initial therapy with an anthracycline-based chemotherapy regimen and has achieved a subsequent partial remission (PR) or a complete remission (CR) following a salvage chemotherapy regimen. * Any subject with NHL that was initially refractory to an anthracycline-based chemotherapy regimen but who has achieved a PR or CR following a salvage chemotherapy regimen. * Any subject with an initial International Prognostic Index (IPI) score 4-5 who achieved a PR or any CR following an anthracycline-based chemotherapy regimen except subjects with Mantle cell, T cell and Natural Killer (NK) cell pathologies. * Subjects with Mantle cell, T cell and NK cell lymphoma may be enrolled if they have PR or CR after initial therapy. * Any subject that has relapsed or progressed following previous autologous HSCT. Subjects with HL to be included: * Any subject with HL that had relapsed or progressed following initial therapy with an multi-drug chemotherapy regimen and has achieved a subsequent PR or a CR following a salvage chemotherapy regimen. * Any subject with HL that is initially refractory to a multi-drug chemotherapy regimen but who has achieved a PR or CR following a salvage chemotherapy regimen. * Any subject that has relapsed or progressed following previous autologous HSCT.
Exclusion criteria
* Any subject with chemoresistant disease by demonstration of less than PR to most recent chemotherapy, and any subject with prior treatment history of autologous HSCT or high-dose chemotherapy with stem cell rescue for any medical reason will be excluded. Excluded will also be subjects with existing or active central nervous system lymphoma or human immunodeficiency virus related lymphoma, unacceptable organ function, or uncontrolled infections.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Progression Events in 2 Years. | 2 years | The time of Progression-Free Survival (PFS) was defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Death Events in 2 Years. | 2 years | The time of overall survival was defined as the time from transplantation to death of all causes. |
| Number of Transplant-related Death Events Until Day 100. | Day 100 | Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100. |
| Overall Response Rate | Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination) | The overall response status is complete response and not complete response (partial remission, primary refractory/primary induction failure, stable disease, progressive disease, and relapse) at Baseline and each of the scheduled follow-up time points. |
Countries
Canada, United States
Participant flow
Recruitment details
A multicenter (43 trial sites in United States and Canada), single-arm, open-label, phase 2 exploratory trial to evaluate clinical outcomes following pharmacokinetic (PK)-directed intravenous (IV) busulfan therapy in 207 participants with Non-Hodgkin's and Hodgkin's lymphoma were evaluated.
Pre-assignment details
Test dose of 0.8 mg/kg of IV busulfan was administered (2-hour continuous infusion) 1 day between Days -14 and -11 for PK analysis to inform subsequent dosing. The conditioning regimen consisted of IV busulfan on Days -8 to -5, etoposide on Day -4, and cyclophosphamide on Days -3 and -2, followed by stem cell infusion on Day 0.
Participants by arm
| Arm | Count |
|---|---|
| Hodgkin's/Non-Hodgkin's Lymphoma (≤ 65 Years) Participants with Hodgkin's or Non-Hodgkins lymphoma whose age was ≤ 65 years; who received a test dose of 0.8 mg/kg of IV busulfan between Days -14 and -11; and recieved conditioning regimen of IV busulfan once daily on Days -8 to -5, etoposide on Day -4, and cyclophosphamide on Days -3 and -2, followed by stem cell infusion on Day 0. | 188 |
| Hodgkin's/Non-Hodgkin's Lymphoma (> 65 Years) Participants with Hodgkin's or Non-Hodgkins lymphoma whose age was \> 65 years; who received a test dose of 0.8 mg/kg of IV busulfan between Days -14 and -11; and recieved conditioning regimen of IV busulfan once daily on Days -8 to -5, etoposide on Day -4, and cyclophosphamide on Days -3 and -2, followed by stem cell infusion on Day 0. | 19 |
| Total | 207 |
Baseline characteristics
| Characteristic | Hodgkin's/Non-Hodgkin's Lymphoma (≤ 65 Years) | Hodgkin's/Non-Hodgkin's Lymphoma (> 65 Years) | Total |
|---|---|---|---|
| Age, Continuous Years | 46.5 Years STANDARD_DEVIATION 13.1 | 68.5 Years STANDARD_DEVIATION 2.3 | 48.5 Years STANDARD_DEVIATION 14 |
| Sex: Female, Male Female | 66 Participants | 2 Participants | 68 Participants |
| Sex: Female, Male Male | 122 Participants | 17 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 190 / 207 |
| serious Total, serious adverse events | 90 / 207 |
Outcome results
Primary
Number of Progression Events in 2 Years.
The time of Progression-Free Survival (PFS) was defined as the time from transplantation to the occurrence of the event that was death or first recurrence of progressive disease.
Time frame: 2 years
Population: Participants receiving at least 1 PK-directed IV busulfan dose followed by autologous hematopoietic stem cell transplant are included in the Intent-to-treat (ITT) data set. Four participants (of 207) did not continue to the conditioning regimen after receiving the PK test dose and were excluded from ITT data set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hodgkin's Lymphoma (≤ 65 Years) | Number of Progression Events in 2 Years. | 41 Event |
| Hodgkin's Lymphoma (> 65 Years) | Number of Progression Events in 2 Years. | 1 Event |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Number of Progression Events in 2 Years. | 46 Event |
| Non-Hodgkin's Lymphoma (> 65 Years) | Number of Progression Events in 2 Years. | 8 Event |
Secondary
Number of Death Events in 2 Years.
The time of overall survival was defined as the time from transplantation to death of all causes.
Time frame: 2 years
Population: Participants receiving at least 1 PK-directed IV busulfan dose followed by autologous hematopoietic stem cell transplant are included in the ITT data set. Four participants (of 207) did not continue to the conditioning regimen after receiving the PK test dose and were excluded from ITT data set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hodgkin's Lymphoma (≤ 65 Years) | Number of Death Events in 2 Years. | 13 Deaths |
| Hodgkin's Lymphoma (> 65 Years) | Number of Death Events in 2 Years. | 1 Deaths |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Number of Death Events in 2 Years. | 28 Deaths |
| Non-Hodgkin's Lymphoma (> 65 Years) | Number of Death Events in 2 Years. | 6 Deaths |
Secondary
Number of Transplant-related Death Events Until Day 100.
Transplant-related mortality was defined as death due to any cause other than disease relapse/progression up until Day 100.
Time frame: Day 100
Population: Participants receiving at least 1 PK-directed IV busulfan dose followed by autologous hematopoietic stem cell transplant are included in the ITT data set. Four participants (of 207) did not continue to the conditioning regimen after receiving the PK test dose and were excluded from ITT data set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hodgkin's Lymphoma (≤ 65 Years) | Number of Transplant-related Death Events Until Day 100. | 1 Transplant-related death |
| Hodgkin's Lymphoma (> 65 Years) | Number of Transplant-related Death Events Until Day 100. | 1 Transplant-related death |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Number of Transplant-related Death Events Until Day 100. | 5 Transplant-related death |
| Non-Hodgkin's Lymphoma (> 65 Years) | Number of Transplant-related Death Events Until Day 100. | 3 Transplant-related death |
Secondary
Overall Response Rate
The overall response status is complete response and not complete response (partial remission, primary refractory/primary induction failure, stable disease, progressive disease, and relapse) at Baseline and each of the scheduled follow-up time points.
Time frame: Baseline, Day 100, Month 6, 12, 24, Early termination and End of Trial (within 30 days of the trial termination)
Population: Participants receiving at least 1 PK-directed IV busulfan dose followed by autologous hematopoietic stem cell transplant are included in the ITT data set. Four participants (of 207) did not continue to the conditioning regimen after receiving the PK test dose and were excluded from ITT data set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 12-Not Complete Response (N=32, 0, 88, 0) | 10 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Baseline-Complete Response (N=65, 0, 121, 16) | 35 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 24-Not Complete Response (N=13, 0, 28, 0) | 2 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 6-Complete Response (N=45, 0, 98, 11) | 30 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Day 100-Complete Response (N=57, 0, 114, 12) | 35 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 24-Complete Response (N=13, 0, 28, 6) | 11 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Early Term-Not Complete Response (N=40, 0, 41, 5) | 38 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 6-Not Complete Response (N=45, 0, 98, 11) | 15 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | End of Trial-Not Complete Response(N=22, 0, 71, 9) | 2 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Baseline-Not Complete Response (N=65, 1, 121, 16) | 30 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | End of Trial-Complete Response (N=22, 0, 71, 9) | 20 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 12-Complete Response (N=32, 0, 88, 8) | 22 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Day 100-Not Complete Response (N=57, 0, 114, 12) | 22 Participants |
| Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Early Term-Complete Response (N=40, 0, 41, 0) | 2 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Baseline-Not Complete Response (N=65, 1, 121, 16) | 1 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 12-Not Complete Response (N=32, 0, 88, 0) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 24-Not Complete Response (N=13, 0, 28, 0) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 24-Complete Response (N=13, 0, 28, 6) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | End of Trial-Complete Response (N=22, 0, 71, 9) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Day 100-Complete Response (N=57, 0, 114, 12) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Baseline-Complete Response (N=65, 0, 121, 16) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Day 100-Not Complete Response (N=57, 0, 114, 12) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Early Term-Not Complete Response (N=40, 0, 41, 5) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 6-Complete Response (N=45, 0, 98, 11) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | End of Trial-Not Complete Response(N=22, 0, 71, 9) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 6-Not Complete Response (N=45, 0, 98, 11) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Early Term-Complete Response (N=40, 0, 41, 0) | 0 Participants |
| Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 12-Complete Response (N=32, 0, 88, 8) | 0 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Baseline-Not Complete Response (N=65, 1, 121, 16) | 49 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Baseline-Complete Response (N=65, 0, 121, 16) | 72 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Day 100-Complete Response (N=57, 0, 114, 12) | 85 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Day 100-Not Complete Response (N=57, 0, 114, 12) | 29 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 6-Complete Response (N=45, 0, 98, 11) | 84 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 6-Not Complete Response (N=45, 0, 98, 11) | 14 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 12-Complete Response (N=32, 0, 88, 8) | 71 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 12-Not Complete Response (N=32, 0, 88, 0) | 17 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 24-Complete Response (N=13, 0, 28, 6) | 26 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | End of Trial-Not Complete Response(N=22, 0, 71, 9) | 6 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Month 24-Not Complete Response (N=13, 0, 28, 0) | 2 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Early Term-Complete Response (N=40, 0, 41, 0) | 4 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | Early Term-Not Complete Response (N=40, 0, 41, 5) | 37 Participants |
| Non-Hodgkin's Lymphoma (≤ 65 Years) | Overall Response Rate | End of Trial-Complete Response (N=22, 0, 71, 9) | 65 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 12-Complete Response (N=32, 0, 88, 8) | 8 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 6-Not Complete Response (N=45, 0, 98, 11) | 2 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Early Term-Not Complete Response (N=40, 0, 41, 5) | 5 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Early Term-Complete Response (N=40, 0, 41, 0) | 0 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 6-Complete Response (N=45, 0, 98, 11) | 9 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Day 100-Not Complete Response (N=57, 0, 114, 12) | 4 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Baseline-Complete Response (N=65, 0, 121, 16) | 12 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Day 100-Complete Response (N=57, 0, 114, 12) | 8 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Baseline-Not Complete Response (N=65, 1, 121, 16) | 4 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 24-Complete Response (N=13, 0, 28, 6) | 6 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | End of Trial-Not Complete Response(N=22, 0, 71, 9) | 1 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 12-Not Complete Response (N=32, 0, 88, 0) | 0 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | End of Trial-Complete Response (N=22, 0, 71, 9) | 8 Participants |
| Non-Hodgkin's Lymphoma (> 65 Years) | Overall Response Rate | Month 24-Not Complete Response (N=13, 0, 28, 0) | 0 Participants |