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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Gemcitabine
Melphalan
ASCT
Sponsored by
AHS Cancer Control Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hodgkin's Lymphoma - Relapsed/Refractory focused on measuring eligible for high-dose therapy and stem cell transplantation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tom Baker Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Gemcitabine/Melphalan Condition + ASCT

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Overall survival
The goal of this study is to improve overall 3-year PFS rate by 15% with the melphalan gemcitabine conditioning.
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).
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
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.
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
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).

Full Information

First Posted
October 30, 2014
Last Updated
March 24, 2023
Sponsor
AHS Cancer Control Alberta
Collaborators
Tom Baker Cancer Centre
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1. Study Identification

Unique Protocol Identification Number
NCT02295722
Brief Title
GEMHDM2014 : Gem-HDM HDT and ASCT for Relapsed/ Refractory Lymphoma
Acronym
GEMHDM2014
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
It did not show a significant benefit to justify completing the full target accrual.
Study Start Date
April 2015 (undefined)
Primary Completion Date
January 2023 (Actual)
Study Completion Date
January 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AHS Cancer Control Alberta
Collaborators
Tom Baker Cancer Centre

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin's Lymphoma - Relapsed/Refractory, Non-Hodgkin's Lymphoma - Aggressive, Follicular Lymphoma
Keywords
eligible for high-dose therapy and stem cell transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Gemcitabine/Melphalan Condition + ASCT
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
gemcitabine 1.5 g/m2 INFUSED
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
200 mg/m2
Intervention Type
Other
Intervention Name(s)
ASCT
Intervention Description
Day 0 - Stem cell infusion
Primary Outcome Measure Information:
Title
Progression free survival of relapsed/refractory lymphoma patients treated with infusional gemcitabine, high dose melphalan (Gem-Mel) and ASCT
Description
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.
Time Frame
3 years
Title
Grade 3-4 Hematological Toxicity
Description
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.
Time Frame
3 YEARS
Secondary Outcome Measure Information:
Title
Overall survival
Description
The goal of this study is to improve overall 3-year PFS rate by 15% with the melphalan gemcitabine conditioning.
Time Frame
3 Years
Title
Cost Effectiveness
Description
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).
Time Frame
3 Years
Title
Measure of Melphalan pharmacokinetics, AUC (area under curve)
Description
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
Time Frame
3 Years
Title
Evaluation of relationship between clinical factors and drug exposure in treatment of Gemcitabine/Melphalan with ASCT (autologous stem cell transplantation)
Description
The number of patients with adverse events as a measure of safety and tolerability.
Time Frame
3 years
Title
Evaluation of relation between drug exposure and non-hematological toxicity and progression free survival
Description
Drug exposure as measured by area under the curve related to number of patients with adverse events (non-hematological toxicity) and progression-free survival
Time Frame
3 years
Title
Safety Outcomes assessed adverse events as a measure of safety and tolerability
Description
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).
Time Frame
3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to provide written informed consent Age over 18 years Relapsed/refractory lymphoma after at least 1 prior chemotherapy treatment: Hodgkin's lymphoma Aggressive non-Hodgkin's lymphoma Follicular lymphoma Chemosensitive disease at time of transplantation (i.e. partial response or better to salvage chemotherapy) ECOG (Eastern Cooperative Oncology Group) performance 0-2 Adequate organ function: Cardiac: LVEF (left ventricular ejection fraction)>40% Pulmonary: FEV1 (forced expiratory volume at one second) and DLCO (diffusing capacity of lung for carbon monoxide)>60% predicted Renal: creatinine <150 µmol/L unless caused by ureteric obstruction from lymphoma 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: Clinically significant active infection Active secondary central nervous system disease Other serious co-morbid illness that would compromise study participation. Pregnant or lactating females Prior HDCT/ASCT
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MONA SHAFEY, MD
Organizational Affiliation
Tom Baker Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tom Baker Cancer Center
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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

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