GEMHDM2014 : Gem-HDM HDT and ASCT for Relapsed/ Refractory Lymphoma (GEMHDM2014)
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|ClinicalTrials.gov Identifier: NCT02295722|
Recruitment Status : Recruiting
First Posted : November 20, 2014
Last Update Posted : June 16, 2017
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin's Lymphoma - Relapsed/Refractory Non-Hodgkin's Lymphoma - Aggressive Follicular Lymphoma||Drug: Gemcitabine Drug: Melphalan Other: ASCT||Phase 1 Phase 2|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Infusional Gemcitabine and High-dose Melphalan (HDM) Conditioning Prior to (ASCT) Autologous Stem Cell Transplantation for Patients With Relapsed/Refractory Lymphoma|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||January 2018|
Experimental: Gemcitabine/Melphalan Condition + ASCT
Day -1 -
•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.
gemcitabine 1.5 g/m2 INFUSED
Day 0 - Stem cell infusion
- Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT [ Time Frame: 3 years ]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.
- Grade 3-4 Hematological Toxicity [ Time Frame: 3 YEARS ]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.
- Overall survival [ Time Frame: 3 Years ]The goal of this study is to improve overall 3-year PFS rate by 15% with the melphalan gemcitabine conditioning.
- Cost Effectiveness [ Time Frame: 3 Years ]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).
- Measure of Melphalan pharmacokinetics, AUC (area under curve) [ Time Frame: 3 Years ]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
- Evaluation of relationship between clinical factors and drug exposure in treatment of Gemcitabine/Melphalan with ASCT (autologous stem cell transplantation) [ Time Frame: 3 years ]The number of patients with adverse events as a measure of safety and tolerability.
- Evaluation of relation between drug exposure and non-hematological toxicity and progression free survival [ Time Frame: 3 years ]Drug exposure as measured by area under the curve related to number of patients with adverse events (non-hematological toxicity) and progression-free survival
- Safety Outcomes assessed adverse events as a measure of safety and tolerability [ Time Frame: 3 years ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02295722
|Contact: MONA SHAFEY, MDfirstname.lastname@example.org|
|Tom Baker Cancer Center||Recruiting|
|Calgary, Alberta, Canada, T2N 4N2|
|Contact: Mamta Kantharia 403-521-3419 Mamta.Kantharia@albertahealthservices.ca|
|Principal Investigator:||MONA SHAFEY, MD||Tom Baker Cancer Centre|