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It did not show a significant benefit to justify completing the full target accrual.
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| Name | Class |
|---|---|
| Tom Baker Cancer Centre | OTHER |
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Objective of study: To evaluate the safety and efficacy of infusional gemcitabine prior to HDM (high-dose melphalan) as HDCT (High Dose Chemotherapy) followed by autologous stem cell transplantation in patients with relapsed/refractory lymphoma.
High-dose chemotherapy with autologous stem cell transplantation is the current standard of care for patients with chemosensitive relapsed Hodgkin's lymphoma and aggressive non-Hodgkin's lymphoma, and is an established effective therapy for patients with relapsed follicular lymphoma. Disease relapse remains a major problem, occurring in 50% of these patients, particularly in patients with primary refractory disease or other high-risk features. The addition of gemcitabine to single-agent melphalan as a high-dose conditioning regimen presents a promising combination that may lead to improvements in EFS (Event free survival). If this trial gives encouraging results, it may lead to a phase III trial evaluating this treatment strategy.
Drug exposure would be AUC (area under curve) and clinical factors would be things like obesity, renal function, disease characteristics.
We would be looking at the safety outcomes - i.e. adverse events as a measure of safety and tolerability. The adverse events would be non-hematological toxicities (any) and whether or not it is related to AUC. AUC in relationship to PFS (progression free survival) is also important (we want to know if we need to adjust dose to improve PFS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Gemcitabine/Melphalan Condition + ASCT | Experimental | Day -1 -
Day 0 •Stem cell infusion Patients will be assigned a dose level using the continual reassessment method based on the toxicity data available at the time of their enrollment. The dosing will start at 1.5 g/m2 and will increase by 0.5 mg/m2 at each level to a maximum of 2.5 g/m2. Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gemcitabine | Drug | gemcitabine 1.5 g/m2 INFUSED |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT | The goal is to improve overall 3-year PFS by 15% over what would be expected with standard conditioning regimens. Patients will be stratified into 3 groups according to disease: (a) relapsed/refractory Hodgkins's lymphoma, (b) relapsed/refractory aggressive non-Hodgkin's lymphoma, and (c) relapsed/refractory follicular lymphoma. Grade 3-4 non-hematological toxicity will be defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4. | 3 years |
| Grade 3-4 Hematological Toxicity | Assessment of Dose-limiting toxicity is defined as grade 3 mucositis or skin toxicity lasting more than 3 days before downgrading, or any grade 4 non-hematological toxicity. | 3 YEARS |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival | The goal of this study is to improve overall 3-year PFS rate by 15% with the melphalan gemcitabine conditioning. | 3 Years |
| Cost Effectiveness | Cost-effectiveness as measured by in-hospital costs of Gemcitabine-Melphalan relative to historical controls treated in Calgary with BEAM or Melphalan+/-TBI (Total Body Irradiation). |
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Inclusion Criteria:
Ability to provide written informed consent
Age over 18 years
Relapsed/refractory lymphoma after at least 1 prior chemotherapy treatment:
Chemosensitive disease at time of transplantation (i.e. partial response or better to salvage chemotherapy)
ECOG (Eastern Cooperative Oncology Group) performance 0-2
Adequate organ function:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MONA SHAFEY, MD | Tom Baker Cancer Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tom Baker Cancer Center | Calgary | Alberta | T2N 4N2 | Canada |
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| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000093542 | Gemcitabine |
| D008558 | Melphalan |
| ID | Term |
|---|---|
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
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| Melphalan |
| Drug |
200 mg/m2 |
|
| ASCT | Other | Day 0 - Stem cell infusion |
|
| 3 Years |
| Measure of Melphalan pharmacokinetics, AUC (area under curve) | Drug exposure would be AUC (area under curve) . Once the dose of gemcitabine has been established, all subsequent patients will receive a uniform HDCT (high dose chemotherapy) regimen. Patients will undergo blood draws for pharmacokinetic testing at the following time points relative to the end of melphalan infusion: 5 minutes, 30 minutes, 1 hour, 3 hours, 5 hours, 7-10 hours, and 18-23 hours. Samples will be processed at the local pharmacokinetics laboratory in Calgary | 3 Years |
| Evaluation of relationship between clinical factors and drug exposure in treatment of Gemcitabine/Melphalan with ASCT (autologous stem cell transplantation) | The number of patients with adverse events as a measure of safety and tolerability. | 3 years |
| Evaluation of relation between drug exposure and non-hematological toxicity and progression free survival | Drug exposure as measured by area under the curve related to number of patients with adverse events (non-hematological toxicity) and progression-free survival | 3 years |
| Safety Outcomes assessed adverse events as a measure of safety and tolerability | Assess adverse events as a measure of safety and tolerability. The adverse events would be non-hematological toxicities (any) and whether or not it is related to AUC. AUC in relationship to PFS is also important (we want to know if we need to adjust dose to improve PFS). | 3 years |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D011743 |
| Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |