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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00566228
• Other study ID #: MC0681
• Secondary ID: P30CA015083MC068
• Status: Completed
• Phase: Phase 3
• Start date: December 2007
• Est. completion date: January 15, 2015

Study information

• Verified date: June 2018
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: January 15, 2015
• Est. primary completion date: January 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Large B-Cell, Diffuse

Intervention

Procedure:
• autologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
• leukapheresis
Stem cells collected

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	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
Primary	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.	Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.
Secondary	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).	Date of infusion to disease progression, relapse, or death from any cause, up to one year
Secondary	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).	Date of infusion to disease progression, relapse, or death from any cause, up to two years
Secondary	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.	date of infusion to death from any cause, up to one year
Secondary	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.	Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
Secondary	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.	5 to 7 days after patient received granulocyte-colony stimulating factor and reached a peripheral CD34 count of 10 cells/microliter or greater