GEMHDM2014 : Gem-HDM HDT and ASCT for Relapsed/ Refractory Lymphoma

Infusional Gemcitabine and High-dose Melphalan (HDM) Conditioning Prior to (ASCT) Autologous Stem Cell Transplantation for Patients With Relapsed/Refractory Lymphoma

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).

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