Two Different Methods of Collecting Stem Cells For an Autologous Stem Cell Transplant in Treating Patients With Diffuse Large Cell Lymphoma

June 6, 2018 updated by: Mayo Clinic

Randomized, Double-Blind Phase III Clinical Trial Comparing Outcomes of Immunologic Autograft Engineering Versus Standard Autograft Collection in Patients Undergoing Autologous Stem Cell Transplantation for Lymphoma

RATIONALE: It is not yet known which method of stem cell collection is best for patients undergoing an autologous stem cell transplant.

PURPOSE: This randomized phase III trial is comparing two different methods of collecting stem cells in patients undergoing stem cell transplant for diffuse large cell lymphoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the therapeutic effect of instrument-driven lymphocyte enrichment of the autograft absolute lymphocyte count (A-ALC) compared to "standard autograft collection" as determined by progression-free survival post-transplantation.

Secondary

  • Determine the profile of immune effector cells of the "lymphocyte enriched autograft" vs "standard autograft" and peripheral blood after autologous stem cell transplant (ASCT) and their impact on post- ASCT immunological reconstitution and clinical endpoints.
  • Perform quantitative and functional analysis of T, B, NK, and dendritic cells from the apheresis product and peripheral blood samples at multiple timepoints after transplantation.
  • Determine and compare the proportion of patients who are progression-free and alive at 1 and 2 years.
  • Determine the differences in overall survival between the two collection method arms.
  • Evaluate and characterize differences in transplantation outcomes (e.g., time to ALC engraftment, incidence of infection, and the CD34 count) between the two collection method arms.

OUTLINE: Patients are stratified according to baseline International Prognostic Factor (≥ 2 factors vs < 2 factors) and PET scan findings prior to transplantation (positive vs negative). Patients receive filgrastim (G-CSF) alone or G-CSF and sargramostim (GM-CSF) daily for stem cell mobilization. Once the peripheral CD34-positive cell count reaches ≥ 10/μL, patients undergo stem cell collection. Patients are then randomized to 1 of 2 treatment arms for standard autologous stem cell transplantation (ASCT).

  • Immunologic autograft engineering: Patients' stem cells are collected according to modified Amicus settings (i.e., MNC OFFSET = 0.0 and RBC = 7.0). Patients undergo ASCT IV on the day of apheresis (lymphocyte enriched autograft).
  • Standard autograft collection: Patients' stem cells are collected according to standard Amicus settings (i.e., MNC OFFSET = 1.5 and RBC OFFSET = 5.0). Patients undergo ASCT IV on the day of apheresis.

Patients undergo blood sample collection periodically for immunological studies. Samples are analyzed for immunophenotyping of immune cell subsets via multicolor flow cytometry, immunoglobulin reconstitution, and functional T-cell immunity.

After completion of study treatment, patients are followed at day 15 post ASCT and then at 3, 6, 9, and 12 months.

Study Type

Interventional

Enrollment (Actual)

122

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

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 to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of diffuse large cell lymphoma

    • Low-grade non-Hodgkin lymphoma transformed to diffuse large cell lymphoma allowed

  • Candidate for with autologous peripheral blood stem cell transplantation

    • Not requiring bone marrow harvest to collect stem cells
    • No chemotherapy with filgrastim ( G-CSF) or mobilization study drug (i.e., AMD3100) needed for mobilization of stem cells

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Cardiac and pulmonary status sufficient to undergo apheresis and stem cell transplantation
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • No active uncontrolled infection requiring antibiotic treatment
  • No comorbid condition which, in view of the investigators, renders the patient at high risk from treatment complications
  • Willing to provide all research blood samples as required by the protocol

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior chemotherapy (rituxan is not considered chemotherapy for the purpose of this study)
  • More than 4 weeks since prior experimental therapy
  • No concurrent enrollment on another experimental protocol during the mobilization phase
  • No concurrent participation in any autologous stem cell transplantation study that is not using the standard conditioning regimens for lymphomas

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Immunologic autograft engineering
Patients' stem cells are collected according to modified Amicus settings (i.e., MNC OFFSET = 0.0 and RBC = 7.0). Patients undergo ASCT IV on the day of apheresis (lymphocyte enriched autograft).
Procedure: autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
Procedure: leukapheresis
Stem cells collected
Active Comparator: Standard autograft collection
Patients' stem cells are collected according to standard Amicus settings (i.e., MNC OFFSET = 1.5 and RBC OFFSET = 5.0). Patients undergo ASCT IV on the day of apheresis.
Procedure: autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
Procedure: leukapheresis
Stem cells collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival
Time Frame: Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.
Progression free survival (PFS) was defined as the time from the date of infusion to disease progression, relapse, or death from any cause. Patients alive without disease progression or relapse were censored at their last disease evaluation or at their secondary primary cancer diagnosis, whichever occurred first. Criteria for Relapsed Disease: Appearance of any new lesion or increase by ≥50% in the size of previously involved sites, ≥50% increase in greatest diameter of any previously identified node >1.0 cm in its short axis or in the sum of the products of diameters (SPD) of more than one node. Criteria for Progressive Disease: ≥50% increase from nadir in the SPD of any previously identified abnormal node or ALC for partial remissions or non-responders, Appearance of any new lesion (≥ 2x2 cm). A log rank test was used to assess whether PFS differed with respect to apheresis collection method.
Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival Rate at 1 Year
Time Frame: Date of infusion to disease progression, relapse, or death from any cause, up to one year
Progression-free survival rate (percentage) at one year is defined as 100 times the number of patients who have not progressed, relapsed and/or died divided by the total number of evaluable patients in each arm. Criteria for Relapsed Disease: Appearance of any new lesion or increase by ≥50% in the size of previously involved sites, ≥50% increase in greatest diameter of any previously identified node >1.0 cm in its short axis or in the SPD of more than one node. Criteria for Progressive Disease: ≥50% increase from nadir in the SPD of any previously identified abnormal node or ALC for partial remissions or non-responders, Appearance of any new lesion (≥ 2x2 cm).
Date of infusion to disease progression, relapse, or death from any cause, up to one year
Progression-free Survival Rate at 2 Years
Time Frame: Date of infusion to disease progression, relapse, or death from any cause, up to two years
Progression-free survival rate (percentage) at two years is defined as 100 times the number of patients who have not progressed, relapsed and/or died divided by the total number of evaluable patients in each arm. Criteria for Relapsed Disease: Appearance of any new lesion or increase by ≥50% in the size of previously involved sites, ≥50% increase in greatest diameter of any previously identified node >1.0 cm in its short axis or in the SPD of more than one node. Criteria for Progressive Disease: ≥50% increase from nadir in the SPD of any previously identified abnormal node or ALC for partial remissions or non-responders, Appearance of any new lesion (≥ 2x2 cm).
Date of infusion to disease progression, relapse, or death from any cause, up to two years
One-year Overall Survival Rate
Time Frame: date of infusion to death from any cause, up to one year
Overall survival (OS) was defined at the time from infusion to death from any cause. The one-year OS rate is defined as the percentage of patients who are still alive after one year. A log rank test was used to assess whether OS differed with respect to apheresis collection method.
date of infusion to death from any cause, up to one year
Median Time to Absolute Lymphocyte Count Engraftment
Time Frame: Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
The time to absolute lymphocyte count (ALC) engraftment will be evaluated and compared between the two arms, where time to ALC engraftment is defined as the time from transplant to the time they achieve ALC > 500.
Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
Median Number of CD34 Cells/kg Infused
Time Frame: 5 to 7 days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater
Five (5) to seven (7) days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater, stem cell collection began. Apheresis collections were to be performed daily. At least 2 x 10^6 CD34 cells/kg were to be collected. Additional collections were at the discretion of the transplantation team. The median number of CD34 cells/kg infused are reported for each arm below.
5 to 7 days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation and Comparison of Immunologic Recovery Within and Between the Arms by Assessing the Quantitative and Functional Immune Effector Cells (T, B, or NK Cells) From the Apheresis Product
Time Frame: Baseline
Evaluation and comparison of immunologic recovery within and between the arms by assessing the quantitative and functional immune effector cells (T, B, or NK cells) from the apheresis product
Baseline

Collaborators and Investigators

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

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Luis F. Porrata, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2007

Primary Completion (Actual)

January 15, 2015

Study Completion (Actual)

January 15, 2015

Study Registration Dates

First Submitted

November 30, 2007

First Submitted That Met QC Criteria

November 30, 2007

First Posted (Estimate)

December 3, 2007

Study Record Updates

Last Update Posted (Actual)

July 9, 2018

Last Update Submitted That Met QC Criteria

June 6, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MC0681 (Other Identifier: Mayo Clinic Cancer Center)
  • P30CA015083 (U.S. NIH Grant/Contract)
  • 07-000789 (Other Identifier: Mayo Clinic IRB)

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.

Clinical Trials on Lymphoma

Clinical Trials on autologous hematopoietic stem cell transplantation

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Mozambique

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe