Hodgkin Disease, Non-Hodgkin Lymphoma
Conditions
Keywords
AMD3100, stem cell mobilization, autologous transplant, Non-Hodgkin Lymphoma, Hodgkin Disease
Brief summary
Participants with non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD) will be assigned to one of 2 arms based on the immunophenotype of their lymphoma. (A)Participants with CD20(-) lymphoma will undergo mobilization with granulocyte colony-stimulating factor (G-CSF) and plerixafor. (B) Participants with CD20(+) lymphomas will undergo mobilization with rituximab, G-CSF, and plerixafor. They will receive a weekly dose of rituximab beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF. Participants in both groups will receive G-CSF twice daily for 4 days. In the evening on Day 4, a dose of plerixafor will be administered. Apheresis will be initiated the next morning. Participants will continue to receive G-CSF twice daily and to receive the evening dose of plerixafor followed by apheresis the next morning for up to a total of 4 aphereses or until ≥5\*10\^6 CD34+ cells/kg are collected. Participants who are transplanted will be monitored for the time to polymorphonuclear leukocytes (PMN), platelets (PLT), and lymphocyte engraftment. Follow-up assessments will be done at 100 days, and 6 and 12 months post-transplantation.
Detailed description
This is a single-center, 2-arm, non-randomized, open-label study to evaluate the safety of plerixafor when used in combination with rituximab (Rituxan®) and granulocyte colony-stimulating factor (G-CSF) in patients with relapsed or refractory Hodgkin disease (HD) or non-Hodgkin lymphoma (NHL). Participants will be assigned to one of 2 arms based on the immunophenotype of their lymphoma. (A)Participants with CD20(-) lymphoma will undergo mobilization with G-CSF and plerixafor. (B) Participants with CD20(+) lymphomas will undergo mobilization with rituximab, G-CSF, and plerixafor. They will receive a weekly dose of 375 mg/m2 rituximab by intravenous (iv) infusion beginning 1 week prior to, and continuing until 2 weeks after, the first dose of G-CSF. Participants in both groups will receive 7.5 µg/kg G-CSF twice daily (morning and evening) for 4 days. In the evening (approximately 10:00 pm) on Day 4, a dose of plerixafor (240 µg/kg) will be administered. Apheresis will be initiated the next morning, approximately 10 to 11 hours after plerixafor is given. Participants will continue to receive G-CSF twice daily and to receive the evening dose of plerixafor followed by apheresis the next morning for up to a total of 4 aphereses or until ≥5\*10\^6 CD34+ cells/kg are collected. Participants with an adequate number of autologous peripheral blood stem cells (PBSCs) collected by apheresis will be admitted to the study center for the administration of high-dose chemotherapy and autologous transplantation. After transplantation, the times to PMN, PLT, and lymphocyte engraftment will be measured. Participants will remain hospitalized until they achieve an absolute granulocyte count of \>500/µl in the peripheral blood. Graft durability will be assessed at 100 days, and 6 and 12 months post-transplantation. This study was previously posted by AnorMED, Inc. In November 2006, AnorMED, Inc. was acquired by Genzyme Corporation. Genzyme Corporation is the sponsor of the trial.
Interventions
Participants underwent mobilization with G-CSF (7.5 µg/kg twice daily) for 4 days, administered by subcutaneous (sc) injection. On the evening of Day 4, participants received a dose of plerixafor (240 µg/kg), administered by SC injection. On Day 5, participants returned to the clinic and received a morning dose of G-CSF (7.5 µg/kg) and underwent apheresis approximately 10 to 11 hours after the dose of plerixafor. Participants were to continue to receive G-CSF twice daily and to receive the evening dose of plerixafor followed by apheresis the following morning for a maximum of 4 aphereses or until ≥ 5\*10\^6 CD34+ cells/kg were collected.
BIOLOGICALrituximab
Participants were given a weekly dose of rituximab 375mg/m2 by intravenous infusion for 1 week prior to and continuing until 2 weeks after the first dose of G-CSF.
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
(abbreviated list): * Histological diagnosis of diffuse large cell lymphoma, B-cell, T-cell or anaplastic histologies; peripheral T-cell lymphoma; small non-cleaved Burkitt-like lymphoma; or Hodgkin disease. NOTE: Participants diagnosed at a facility outside of Emory University will have their diagnosis confirmed by Emory University pathologists prior to being enrolled in this study. * Eligible for autologous transplantation. * History of relapse of lymphoma following initial treatment with an anthracycline-containing regimen or disease that is refractory or progresses during initial therapy with an anthracycline-containing regimen. * Immunophenotyping of the lymphoma at the time of diagnosis or relapse using flow cytometry or immunohistochemistry. * Presence of clinically- and/or radiologically-documented, measurable, and/or evaluable disease at the time of relapse. * Received 2 cycles of salvage chemotherapy. * Complete response (i.e., normal physical examination, lymph nodes, lymph node masses, and bone marrow) or a partial response (i.e., decrease of ≧50% in the size of lymph nodes or lymph node masses or decrease in size of liver/spleen on physical exam) to at least one cycle of a salvage chemotherapy regimen. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. * Absolute granulocytes count ≧1.0\*10\^9/l. * Platelet count ≧75\*10\^9/l. * Aspartate aminotransferase (AST) or alanine transaminase (ALT) ≦2.5 times the upper limit of normal (ULN) or ≦5 times the ULN if liver involvement with lymphoma. * Life expectancy of at least 3 months. * \>4 weeks since last cycle of chemotherapy. * Patient has recovered from all acute toxic effects of prior chemotherapy. * Signed informed consent.
Exclusion criteria
(abbreviated list): * A second active malignancy (other than basal cell carcinoma of the skin). * Uncontrolled central nervous system involvement by lymphoma. * Positive/history of retroviral infection (HIV, HTLV-1). * Active infection requiring antibiotics during planned lymphoma-related therapy. * Previous treatment with high-dose chemotherapy or cytokine mobilization and hematopoietic progenitor cell transplantation. * Continued evidence by morphology and flow cytometry of bone marrow involvement after at least one cycle of salvage chemotherapy. * ≥3 cycles of salvage chemotherapy following documentation of lymphoma relapse or disease progression. * (In patients with CD20(+) lymphoma) History of severe hypersensitivity reactions to rituximab. * Positive pregnancy test in female patients. * Lactating female patients. * Previously received experimental therapy within 4 weeks of enrolling in this protocol or currently enrolled in another experimental protocol during G-CSF Mobilization Phase. * Creatinine \>1.5 times the ULN. * Bilirubin \>1.5 times the ULN. * Ejection fraction \<45%. * Diffusion capacity of the lung for carbon monoxide (DLCO) \<50%. * Patients of childbearing potential unwilling to implement adequate birth control. * A co-morbid condition that renders the patient at high risk from treatment complications. * Residual acute medical condition resulting from prior chemotherapy. * Documented history of ventricular arrhythmias during the last 3 years. * Fever (temperature \>38 °C/100.4 °F). * Actual body weight exceeds 175% of ideal body weight. * Participants who have deterioration of their clinical status or laboratory parameters between the time of enrolment and transplant (such that they no longer meet entry criteria) may be removed from study at the discretion of the treating physician, principal investigator, or sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Adverse Events (AEs) | Day 1 and up to Day 59 (maximum time before start of chemotherapy) | Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization in participants with CD20- lymphoma or start of rituximab in participants with CD20+ lymphoma) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for seriousness and relatedness to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration | Days 4-5 | Fold Increase = (Pre-Apheresis CD34+ cells/Pre-Plerixafor CD34+ cells). |
| Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg | Days 5-8 | Median number of apheresis days in each treatment arm to collect a minimum of 3\*10\^6 CD34+ cells/kg. |
| Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg | Days 5-8 | Median number of apheresis days in each treatment arm to reach the target of 5\*10\^6 CD34+ cells/kg. |
| Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | Days post transplantation (approximately Day 40) | Median number of days from transplantation to PMN engraftment which was defined as PMN counts ≥0.5\*10\^9/L for 3 consecutive days or ≥1.0\*10\^9/L for 1 day. Time to engraftment corresponded to the first day that the criteria were met. |
| Median Number of Days to Platelet (PLT) Engraftment | Days post transplantation (approximately Day 40) | Median number of days from transplantation to PLT engraftment which was defined as platelet counts ≥20\*10\^9/L without transfusion for the preceding 7 days or platelet counts ≥50\*10\^9/L for one day. Time to engraftment corresponded to the first day that the criteria were met. |
| Median Cumulative Number of CD34+ Cells Collected During Apheresis | Days 5-8 | Median total number of CD34+ cells collected during apheresis. |
| Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant | Approximately 7 months (6 months post-transplant) | — |
| Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant | 13 months (12 months post-transplant) | — |
| The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day | Day 5 | — |
| Number of Participants With Durable Engraftment 12 Months After Transplantation | Approximately 13 months (12 months post-transplant ) | The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts. |
| Median Number of Days to Lymphocyte Engraftment | Days post transplantation (approximately Day 40) | Median number of days from transplantation to lymphocyte engraftment which was defined as lymphocyte counts ≥5\*10\^8/L. Time to engraftment corresponded to the first day that criteria were met. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| G-CSF and Plerixafor Participants with CD20- lymphoma received granulocyte colony-stimulating factor (G-CSF) and plerixafor | 15 |
| G-CSF and Plerixafor + Rituximab Participants with CD20+ lymphoma received rituximab, G-CSF, and plerixafor | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Participant Failed Mobilization | 1 | 0 |
Baseline characteristics
| Characteristic | G-CSF and Plerixafor + Rituximab | Total | G-CSF and Plerixafor |
|---|---|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 14.9 | 42.9 years STANDARD_DEVIATION 13.5 | 39.3 years STANDARD_DEVIATION 11.3 |
| Disease Diagnosis Hodgkin disease (HD) | 4 Participants | 18 Participants | 14 Participants |
| Disease Diagnosis Non-Hodgkin lymphoma (NHL) | 11 Participants | 12 Participants | 1 Participants |
| Race/Ethnicity, Customized African-American | 1 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 10 Participants | 22 Participants | 12 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Female | 3 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
Summary of Adverse Events (AEs)
Number of participants with adverse events (AEs) collected from Day 1 (start of G-CSF mobilization in participants with CD20- lymphoma or start of rituximab in participants with CD20+ lymphoma) to the day before starting chemotherapy. AEs were graded by the investigator using the World Health Organization (WHO) Adverse Event Grading Scale and were assessed for seriousness and relatedness to study treatment.
Time frame: Day 1 and up to Day 59 (maximum time before start of chemotherapy)
Population: Safety Population: all participants who received at least 1 dose of study drug (G-CSF, plerixafor, or rituximab)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | Participants Reporting at Least 1 AE | 9 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | Participant Count of Mild AEs | 7 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | Participant Count of Moderate AEs | 2 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | Participant Count of Severe AEs | 0 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | Participant Count of Life-Threatening AEs | 0 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | AEs by Relationship - Not Related | 1 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | AEs by Relationship - Probably Not Related | 3 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | AEs by Relationship - Possibly Related | 0 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | AEs by Relationship - Probably Related | 2 participants |
| G-CSF and Plerixafor | Summary of Adverse Events (AEs) | AEs by Relationship - Definitely Related | 3 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | AEs by Relationship - Possibly Related | 5 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | Participants Reporting at Least 1 AE | 13 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | AEs by Relationship - Not Related | 0 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | Participant Count of Mild AEs | 12 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | AEs by Relationship - Definitely Related | 1 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | Participant Count of Moderate AEs | 0 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | AEs by Relationship - Probably Not Related | 4 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | Participant Count of Severe AEs | 0 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | AEs by Relationship - Probably Related | 3 participants |
| G-CSF and Plerixafor + Rituximab | Summary of Adverse Events (AEs) | Participant Count of Life-Threatening AEs | 1 participants |
Secondary
Median Cumulative Number of CD34+ Cells Collected During Apheresis
Median total number of CD34+ cells collected during apheresis.
Time frame: Days 5-8
Population: Full Analysis Set (FAS) includes all participants who received at least 1 dose of plerixafor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Cumulative Number of CD34+ Cells Collected During Apheresis | 7.4 CD34+ cells (*10^6 / kg) |
| G-CSF and Plerixafor + Rituximab | Median Cumulative Number of CD34+ Cells Collected During Apheresis | 6.4 CD34+ cells (*10^6 / kg) |
Secondary
Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration
Fold Increase = (Pre-Apheresis CD34+ cells/Pre-Plerixafor CD34+ cells).
Time frame: Days 4-5
Population: Evaluable population of participants with peripheral blood CD34+ measurements on Days 4 and 5.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration | 2.4 fold increase |
| G-CSF and Plerixafor + Rituximab | Median Fold Increase in the Number of CD34+ Cells After Plerixafor Administration | 2.5 fold increase |
Secondary
Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant
Time frame: Approximately 7 months (6 months post-transplant)
Population: Evaluable population of participants who received a stem cell transplant and had assessment performed 6 months post-transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant | 155.00 cells / μL |
| G-CSF and Plerixafor + Rituximab | Median Level of CD19+CD2-CD14- B-cells Six Months Post-Transplant | 0.50 cells / μL |
Secondary
Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant
Time frame: 13 months (12 months post-transplant)
Population: Evaluable population of participants who received a stem cell transplant and had assessment performed 12 months post-transplant.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant | 322.50 cells / μL |
| G-CSF and Plerixafor + Rituximab | Median Level of CD19+CD2-CD14- B-cells Twelve Months Post-Transplant | 236.00 cells / μL |
Secondary
Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg
Median number of apheresis days in each treatment arm to collect a minimum of 3\*10\^6 CD34+ cells/kg.
Time frame: Days 5-8
Population: Evaluable population of participants who achieved ≥3\*10\^cells/kg collected during apheresis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg | 1.0 days |
| G-CSF and Plerixafor + Rituximab | Median Number of Apheresis Days Required to Reach a Minimum of 3*10^6 CD34+ Cells/kg | 1.0 days |
Secondary
Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg
Median number of apheresis days in each treatment arm to reach the target of 5\*10\^6 CD34+ cells/kg.
Time frame: Days 5-8
Population: Evaluable population of participants who achieved ≥5\*10\^cells/kg collected during apheresis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg | 1.0 days |
| G-CSF and Plerixafor + Rituximab | Median Number of Apheresis Days Required to Reach the Target of 5*10^6 CD34+ Cells/kg | 2.0 days |
Secondary
Median Number of Days to Lymphocyte Engraftment
Median number of days from transplantation to lymphocyte engraftment which was defined as lymphocyte counts ≥5\*10\^8/L. Time to engraftment corresponded to the first day that criteria were met.
Time frame: Days post transplantation (approximately Day 40)
Population: Evaluable population of participants who received a stem cell transplant and had lymphocyte engraftment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Number of Days to Lymphocyte Engraftment | 14.5 days |
| G-CSF and Plerixafor + Rituximab | Median Number of Days to Lymphocyte Engraftment | 14.0 days |
Secondary
Median Number of Days to Platelet (PLT) Engraftment
Median number of days from transplantation to PLT engraftment which was defined as platelet counts ≥20\*10\^9/L without transfusion for the preceding 7 days or platelet counts ≥50\*10\^9/L for one day. Time to engraftment corresponded to the first day that the criteria were met.
Time frame: Days post transplantation (approximately Day 40)
Population: Evaluable population of participants who received a stem cell transplant and had PLT engraftment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Number of Days to Platelet (PLT) Engraftment | 21.0 days |
| G-CSF and Plerixafor + Rituximab | Median Number of Days to Platelet (PLT) Engraftment | 22.0 days |
Secondary
Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment
Median number of days from transplantation to PMN engraftment which was defined as PMN counts ≥0.5\*10\^9/L for 3 consecutive days or ≥1.0\*10\^9/L for 1 day. Time to engraftment corresponded to the first day that the criteria were met.
Time frame: Days post transplantation (approximately Day 40)
Population: Evaluable population of participants who received a stem cell transplant and had PMN engraftment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 13.0 days |
| G-CSF and Plerixafor + Rituximab | Median Number of Days to Polymorphonuclear Leukocyte (PMN) Engraftment | 13.5 days |
Secondary
Number of Participants With Durable Engraftment 12 Months After Transplantation
The number of participants maintaining a durable graft 12 months after autologous transplantation. A durable graft is defined as the maintenance of normal blood counts.
Time frame: Approximately 13 months (12 months post-transplant )
Population: Evaluable population of participants who received a stem cell transplant and had a 12-month assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| G-CSF and Plerixafor | Number of Participants With Durable Engraftment 12 Months After Transplantation | 12 participants |
| G-CSF and Plerixafor + Rituximab | Number of Participants With Durable Engraftment 12 Months After Transplantation | 13 participants |
Secondary
The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day
Time frame: Day 5
Population: Full Analysis Set (FAS) includes all participants who received at least 1 dose of plerixafor.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| G-CSF and Plerixafor | The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day | 2.83 percentage of total cells |
| G-CSF and Plerixafor + Rituximab | The Percentage of CD19+CD3-CD14- B-cells of the Total Cells on the First Apheresis Day | 0.09 percentage of total cells |