Clinical trial NCT00566228: Two Different Methods of Collecting Stem Cells For an Autologous Stem Cell Transplant in Treating Patients With Diffuse Large Cell Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-12-03
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Median Progression-free Survival
timeFrame: Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.
Secondary outcomes:
measure: Progression-free Survival Rate at 1 Year
timeFrame: Date of infusion to disease progression, relapse, or death from any cause, up to one year
measure: Progression-free Survival Rate at 2 Years
timeFrame: Date of infusion to disease progression, relapse, or death from any cause, up to two years
measure: One-year Overall Survival Rate
timeFrame: date of infusion to death from any cause, up to one year
measure: Median Time to Absolute Lymphocyte Count Engraftment
timeFrame: Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
measure: Median Number of CD34 Cells/kg Infused
timeFrame: 5 to 7 days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater
Other outcomes:
measure: 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
timeFrame: Baseline
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Luis F. Porrata, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: Porrata 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.