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

NCT ID: NCT00566228

Last Updated: 2018-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2015-01-15

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.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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).

Group Type: EXPERIMENTAL

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Patients undergo autologous stem cell transplantation

leukapheresis

Intervention Type: PROCEDURE

Stem cells collected

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.

Group Type: ACTIVE_COMPARATOR

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Patients undergo autologous stem cell transplantation

leukapheresis

Intervention Type: PROCEDURE

Stem cells collected

Interventions

autologous hematopoietic stem cell transplantation

Patients undergo autologous stem cell transplantation

Intervention Type: PROCEDURE

leukapheresis

Stem cells collected

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Luis F. Porrata, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 26826432 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30978434 (View on PubMed)

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MC0681

Identifier Type: OTHER

Identifier Source: secondary_id

07-000789

Identifier Type: OTHER

Identifier Source: secondary_id

MC0681

Identifier Type: -

Identifier Source: org_study_id