LymphomaPhase 3NCT00566228
Two Different Methods of Collecting Stem Cells For an Autologous Stem Cell Transplant in Treating Patients With Diffuse Large Cell Lymphoma
A Phase 3 study testing autologous hematopoietic stem cell transplantation and leukapheresis in people with Lymphoma, run by Mayo Clinic at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Lymphoma
- What is being tested?
- autologous hematopoietic stem cell transplantation and leukapheresis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to 15 Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Lymphoma
- Being tested
- autologous hematopoietic stem cell transplantation, leukapheresis
- Keywords
- noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, recurrent adult diffuse large cell lymphoma
- Medical subject headings
- Lymphoma, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous hematopoietic stem cell transplantationProcedure or surgery
Patients undergo autologous stem cell transplantation
leukapheresisProcedure or surgery
Stem cells collected
| Study group | Role | What they receive |
|---|---|---|
| Immunologic autograft engineering | Experimental | 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). Receives: Procedure: autologous hematopoietic stem cell transplantation; Procedure: leukapheresis |
| Standard autograft collection | Active comparator | 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. Receives: Procedure: autologous hematopoietic stem cell transplantation; Procedure: leukapheresis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression-free Survival
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.
Measured: Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.
Secondary outcomes (5)
Progression-free Survival Rate at 1 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).
Measured: Date of infusion to disease progression, relapse, or death from any cause, up to one year
Progression-free Survival Rate at 2 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).
Measured: Date of infusion to disease progression, relapse, or death from any cause, up to two years
One-year Overall Survival Rate
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.
Measured: date of infusion to death from any cause, up to one year
Median Time to Absolute Lymphocyte Count Engraftment
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.
Measured: Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
Median Number of CD34 Cells/kg Infused
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.
Measured: 5 to 7 days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startDec 2007
- Primary completion15 Jan 2015
- Study completion15 Jan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Luis F. Porrata, MD, Study chair, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566228
- Sponsor's protocol ID
- MC0681
- Other IDs
- P30CA015083, MC0681, 07-000789
- Status last verified
- Jun 2018
- First submitted
- 30 Nov 2007
- Last updated
- 9 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Porrata LF, Burgstaler EA, Winters JL, Jacob EK, Gastineau DA, Suman VJ, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Nevala W, Markovic SN. Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2016 Jun;22(6):1017-1023. doi: 10.1016/j.bbmt.2016.01.024. Epub 2016 Jan 27.
PubMed 26826432Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Villasboas JC, Markovic SN. Autograft immune content and survival in non-Hodgkin's lymphoma: A post hoc analysis. Leuk Res. 2019 Jun;81:1-9. doi: 10.1016/j.leukres.2019.03.009. Epub 2019 Apr 4.
PubMed 30978434
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00566228
- Acronym / sponsor ID
- MC0681
- Conditions
- Lymphoma
- Keywords
- noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, recurrent adult diffuse large cell lymphoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2007
- Primary completion
- 15 Jan 2015 (actual)
- Study completion
- 15 Jan 2015 (actual)
- First posted
- 3 Dec 2007 (estimated)
- Results
- Posted 9 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunologic autograft engineering | Experimental | Procedure: autologous hematopoietic stem cell transplantation, Procedure: leukapheresisPatients' 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 | Active comparator | Procedure: autologous hematopoietic stem cell transplantation, Procedure: leukapheresisPatients' 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. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| autologous hematopoietic stem cell transplantationPatients undergo autologous stem cell transplantation | Procedure or surgery | Immunologic autograft engineering, Standard autograft collection |
| leukapheresisStem cells collected | Procedure or surgery | Immunologic autograft engineering, Standard autograft collection |
Primary outcome
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.
5 secondary outcomes
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 at 2 Years
Time frame: 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
Median Time to Absolute Lymphocyte Count Engraftment
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26826432Porrata LF, Burgstaler EA, Winters JL, Jacob EK, Gastineau DA, Suman VJ, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Nevala W, Markovic SN. Immunologic Autograft Engineering and Survival in Non-Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2016 Jun;22(6):1017-1023. doi: 10.1016/j.bbmt.2016.01.024. Epub 2016 Jan 27.
- Derived from this study: PubMed 30978434Porrata LF, Inwards DJ, Ansell SM, Micallef IN, Johnston PB, Villasboas JC, Markovic SN. Autograft immune content and survival in non-Hodgkin's lymphoma: A post hoc analysis. Leuk Res. 2019 Jun;81:1-9. doi: 10.1016/j.leukres.2019.03.009. Epub 2019 Apr 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luis F. Porrata, MD study chair
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing autologous hematopoietic stem cell transplantation and leukapheresis in people with Lymphoma, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00566228, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2018.