Lymphoma
Conditions
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
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.
Interventions
PROCEDUREautologous hematopoietic stem cell transplantation
Patients undergo autologous stem cell transplantation
PROCEDUREleukapheresis
Stem cells collected
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-free Survival | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate at 2 Years | 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). |
| One-year Overall Survival Rate | 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. |
| Progression-free Survival Rate at 1 Year | 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). |
| Median Number of CD34 Cells/kg Infused | 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. |
| Median Time to Absolute Lymphocyte Count Engraftment | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Immunologic Autograft Engineering Patients' stem cells are collected according to modified Amicus settings (i.e., MNC OFFSET = 0.0 and RBC = 7.0). | 61 |
| Standard Autograft Collection Patients' stem cells are collected according to standard Amicus settings (i.e., MNC OFFSET = 1.5 and RBC OFFSET = 5.0). | 60 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Attempt to mobilize stem cells failed | 2 | 2 |
| Overall Study | progressed before infusion could occur | 0 | 1 |
| Overall Study | Unable to collect sufficient CD34 cells | 3 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Immunologic Autograft Engineering | Standard Autograft Collection | Total |
|---|---|---|---|
| Age, Continuous | 58 years | 58 years | 58 years |
| Region of Enrollment United States | 61 Participants | 60 Participants | 121 Participants |
| Sex: Female, Male Female | 16 Participants | 20 Participants | 36 Participants |
| Sex: Female, Male Male | 45 Participants | 40 Participants | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 57 |
| other Total, other adverse events | 22 / 57 | 17 / 57 |
| serious Total, serious adverse events | 0 / 57 | 0 / 57 |
Outcome results
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.
Time frame: Date of infusion to disease progression, relapse, or death from any cause whichever came first, assessed up to 24 months post enrollment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunologic Autograft Engineering | Median Progression-free Survival | NA months |
| Standard Autograft Collection | Median Progression-free Survival | NA months |
p-value: 0.6995% CI: [0.62, 2.08]Log Rank
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.
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunologic Autograft Engineering | Median Number of CD34 Cells/kg Infused | 4.6 x10^6 cells/kg |
| Standard Autograft Collection | Median Number of CD34 Cells/kg Infused | 5.3 x10^6 cells/kg |
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.
Time frame: Up to 30 days after autologous peripheral hematopoietic stem cell transplantation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Immunologic Autograft Engineering | Median Time to Absolute Lymphocyte Count Engraftment | 14 days |
| Standard Autograft Collection | Median Time to Absolute Lymphocyte Count Engraftment | 14 days |
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.
Time frame: date of infusion to death from any cause, up to one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunologic Autograft Engineering | One-year Overall Survival Rate | 91.1 percentage of patients |
| Standard Autograft Collection | One-year Overall Survival Rate | 83.6 percentage of patients |
p-value: 0.679Log Rank
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).
Time frame: Date of infusion to disease progression, relapse, or death from any cause, up to one year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunologic Autograft Engineering | Progression-free Survival Rate at 1 Year | 73.1 percentage of patients |
| Standard Autograft Collection | Progression-free Survival Rate at 1 Year | 65.4 percentage of patients |
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).
Time frame: Date of infusion to disease progression, relapse, or death from any cause, up to two years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunologic Autograft Engineering | Progression-free Survival Rate at 2 Years | 57.9 percentage of patients |
| Standard Autograft Collection | Progression-free Survival Rate at 2 Years | 65.4 percentage of patients |
Other Pre-specified
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
Time frame: Baseline