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

Follicular Lymphoma Clinical Trial

— GEMHDM2014  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02295722
• Other study ID #: GEMHDM2014
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: January 2023

Study information

• Verified date: March 2023
• Source: AHS Cancer Control Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 100
• Est. completion date: January 2023
• Est. primary completion date: January 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma
• Hodgkin's Lymphoma - Relapsed/Refractory
• Lymphoma
• Non-Hodgkin's Lymphoma - Aggressive

Intervention

Drug:
• Gemcitabine
gemcitabine 1.5 g/m2 INFUSED
• Melphalan
200 mg/m2

Other:
• ASCT
Day 0 - Stem cell infusion

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Center	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
AHS Cancer Control Alberta	Tom Baker Cancer Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Secondary	Overall survival	The goal of this study is to improve overall 3-year PFS rate by 15% with the melphalan gemcitabine conditioning.	3 Years
Secondary	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).	3 Years
Secondary	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
Secondary	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
Secondary	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
Secondary	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