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

NCT ID: NCT02295722

Last Updated: 2024-07-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2023-02-28

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).

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine/Melphalan Condition + ASCT

Day -1 -

• IV gemcitabine 1.5-2.5 g/m2 (depending on dose level assigned) administered as a loading bolus of 75 mg/m2, followed by a continuous infusion of 10 mg/m2/min.
• immediately following gemcitabine - IV melphalan 200 mg/m2 over 5 minutes.

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.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

gemcitabine 1.5 g/m2 INFUSED

Melphalan

Intervention Type: DRUG

200 mg/m2

ASCT

Intervention Type: OTHER

Day 0 - Stem cell infusion

Interventions

Gemcitabine

gemcitabine 1.5 g/m2 INFUSED

Intervention Type: DRUG

Melphalan

200 mg/m2

Intervention Type: DRUG

ASCT

Day 0 - Stem cell infusion

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tom Baker Cancer Centre

OTHER

Sponsor Role: collaborator

AHS Cancer Control Alberta

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MONA SHAFEY, MD

Role: PRINCIPAL_INVESTIGATOR

Tom Baker Cancer Centre

Locations

Tom Baker Cancer Center

Calgary, Alberta, Canada

Countries

Canada

Other Identifiers

GEMHDM2014

Identifier Type: -

Identifier Source: org_study_id