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

March 24, 2023 updated by: AHS Cancer Control Alberta

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Gemcitabine
gemcitabine 1.5 g/m2 INFUSED
Drug: Melphalan
200 mg/m2
Other: ASCT
Day 0 - Stem cell infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 years
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.
3 YEARS

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3 Years
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).
3 Years
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
3 Years
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.
3 years
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
3 years
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).
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AHS Cancer Control Alberta

Collaborators

Tom Baker Cancer Centre

Investigators

  • Principal Investigator: MONA SHAFEY, MD, Tom Baker Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2015

Primary Completion (Actual)

January 1, 2023

Study Completion (Actual)

January 1, 2023

Study Registration Dates

First Submitted

October 30, 2014

First Submitted That Met QC Criteria

November 18, 2014

First Posted (Estimate)

November 20, 2014

Study Record Updates

Last Update Posted (Actual)

March 27, 2023

Last Update Submitted That Met QC Criteria

March 24, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEMHDM2014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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