Clinical trial NCT02295722: GEMHDM2014 : Gem-HDM HDT and ASCT for Relapsed/ Refractory Lymphoma
Official title: Infusional Gemcitabine and High-dose Melphalan (HDM) Conditioning Prior to (ASCT) Autologous Stem Cell Transplantation for Patients With Relapsed/Refractory Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hodgkin's Lymphoma - Relapsed/Refractory
Non-Hodgkin's Lymphoma - Aggressive
Follicular Lymphoma
Keywords: eligible for high-dose therapy and stem cell transplantation
Lead sponsor: AHS Cancer Control Alberta
Sponsor class: OTHER
Collaborators: name: Tom Baker Cancer Centre
First posted: 2014-11-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: Inclusion Criteria:

1. Ability to provide written informed consent
2. Age over 18 years
3. Relapsed/refractory lymphoma after at least 1 prior chemotherapy treatment:

   1. Hodgkin's lymphoma
   2. Aggressive non-Hodgkin's lymphoma
   3. Follicular lymphoma
4. Chemosensitive disease at time of transplantation (i.e. partial response or better to salvage chemotherapy)
5. ECOG (Eastern Cooperative Oncology Group) performance 0-2
6. Adequate organ function:

   1. Cardiac: LVEF (left ventricular ejection fraction)\>40%
   2. Pulmonary: FEV1 (forced expiratory volume at one second) and DLCO (diffusing capacity of lung for carbon monoxide)\>60% predicted
   3. Renal: creatinine \<150 µmol/L unless caused by ureteric obstruction from lymphoma
   4. Liver: No evidence of cirrhosis. ALT (Alanine Aminotransferase) and bilirubin \<2x upper limit of normal unless caused by biliary tract obstruction from lymphoma

Exclusion Criteria:

1. Clinically significant active infection
2. Active secondary central nervous system disease
3. Other serious co-morbid illness that would compromise study participation.
4. Pregnant or lactating females
5. Prior HDCT/ASCT

Primary outcomes:
measure: Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT
timeFrame: 3 years
measure: Grade 3-4 Hematological Toxicity
timeFrame: 3 YEARS
Secondary outcomes:
measure: Overall survival
timeFrame: 3 Years
measure: Cost Effectiveness
timeFrame: 3 Years
measure: Measure of Melphalan pharmacokinetics, AUC (area under curve)
timeFrame: 3 Years
measure: Evaluation of relationship between clinical factors and drug exposure in treatment of Gemcitabine/Melphalan with ASCT (autologous stem cell transplantation)
timeFrame: 3 years
measure: Evaluation of relation between drug exposure and non-hematological toxicity and progression free survival
timeFrame: 3 years
measure: Safety Outcomes assessed adverse events as a measure of safety and tolerability
timeFrame: 3 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: Alberta
Study officials:
affiliation: Tom Baker Cancer Centre
name: MONA SHAFEY, MD
role: PRINCIPAL_INVESTIGATOR
References: