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

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ClinicalTrials.gov Identifier: NCT02295722
Recruitment Status : Recruiting
First Posted : November 20, 2014
Last Update Posted : June 16, 2017
Sponsor:
Collaborator:
Tom Baker Cancer Centre
Information provided by (Responsible Party):
AHS Cancer Control Alberta

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.

Condition or disease Intervention/treatment Phase
Hodgkin's Lymphoma - Relapsed/Refractory Non-Hodgkin's Lymphoma - Aggressive Follicular Lymphoma Drug: Gemcitabine Drug: Melphalan Other: ASCT Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 200 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Infusional Gemcitabine and High-dose Melphalan (HDM) Conditioning Prior to (ASCT) Autologous Stem Cell Transplantation for Patients With Relapsed/Refractory Lymphoma
Study Start Date : April 2015
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : January 2018


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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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. 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

  4. 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.

  5. 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

  6. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02295722


Contacts
Contact: MONA SHAFEY, MD mona.shafey@albertahealthservices.ca

Locations
Canada, Alberta
Tom Baker Cancer Center Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Mamta Kantharia    403-521-3419    Mamta.Kantharia@albertahealthservices.ca   
Sponsors and Collaborators
AHS Cancer Control Alberta
Tom Baker Cancer Centre
Investigators
Principal Investigator: MONA SHAFEY, MD Tom Baker Cancer Centre

Responsible Party: AHS Cancer Control Alberta
ClinicalTrials.gov Identifier: NCT02295722     History of Changes
Other Study ID Numbers: GEMHDM2014
First Posted: November 20, 2014    Key Record Dates
Last Update Posted: June 16, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by AHS Cancer Control Alberta:
eligible for high-dose therapy and stem cell transplantation

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Gemcitabine
Melphalan
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists