Hodgkin Disease, Leukemia, Lymphoblastic, Acute, Leukemia, Myelogenous, Chronic, Leukemia, Myeloid, Acute, Lymphocytic Leukemia, Chronic, Lymphoma, Non-Hodgkin, Multiple Myeloma, Myelodysplastic Syndromes
Conditions
Keywords
Plerixafor, Stem cell transplantation, Stem cells, Mobilization
Brief summary
The purpose of this study is to determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.
Detailed description
This study will determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.
Interventions
DRUGAMD3100
PROCEDUREStem Cell Transplant
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Donor criteria: * Donor is 18 to 70 years of age inclusive * If female and of child-bearing age, must be: * non-pregnant, * not breast feeding and * using adequate contraception * Donor is a 6/6 HLA-matched sibling willing to donate peripheral blood stem cell for transplant * Donor must be willing to provide written informed consent. * Adequate cardiac function with no history of congestive heart failure and no history of atrial fibrillation or ventricular tachyarrhythmia. * Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation) * Adequate hepatic function as defined by a total bilirubin \<2x normal or absence of hepatic fibrosis/cirrhosis * Adequate neurologic function as defined by: * No evidence of a severe central or peripheral neurologic abnormality. * No history of cerebrovascular accident or seizure disorder requiring anticonvulsant medication * Must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test. * Must have an ECOG performance status of 0 or 1 * Must demonstrate ability to be compliant with study regimen. * Must not have an active infection at the time of study entry * Not have active alcohol or substance abuse within 6 months of study entry * Not currently enrolled in another investigational agent study * Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with his/her evaluation Recipient criteria: * 18 to 65 years of age inclusive * Willing and has a 6/6 HLA-matched sibling willing to donate PBSC for transplant * Provide signed informed consent * If female and of child-bearing age, must be: * non-pregnant, * not breast feeding, and * using adequate contraception Patient must have one of the following diagnoses: * AML in 1st or subsequent remission or in relapse * ALL in 1st or subsequent remission or in relapse * MDS and intermediate 1 or 2, or high risk by the International Prognostic Scoring System * CML in accelerated or second chronic phase * NHL or HD in 2nd or greater complete remission, partial remission,or refractory relapse * CLL Rai Stage 2-4, failing at least 2 prior regimens * MM Stage 2-3 * Adequate cardiac function with a left ventricular ejection fraction ≥ 40% * Adequate pulmonary function defined as: * No severe or symptomatic restrictive or obstructive lung disease, and * formal pulmonary function testing showing an forced expiratory volume at 1 second (FEV1) ≥50% of predicted and a diffusion capacity of the lung for carbon monoxide (DLCO) ≥40% of predicted, corrected for hemoglobin * Adequate renal function as defined by a serum creatinine clearance of ≥75% of normal (Cockcroft-Gault equation) * Adequate hepatic function as defined by a total bilirubin \<2x normal or absence of hepatic fibrosis/cirrhosis * Adequate neurologic function as defined by no evidence of a severe central or peripheral neurologic abnormality. Patients with a history of previous central nervous system tumor involvement are eligible provided they are without symptoms or signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain * No evidence of active infection at the time of the transplant preparative regimen or at the time of transplantation * Patient must be HIV-1 & 2 antibody, HIV-1 antigen, and HTLV-I & II antibody sero-negative, by FDA licensed test * ECOG performance status of 0 or 1 * Must demonstrate ability to be compliant with medical regimen * Not have active alcohol or substance abuse within 6 months of study entry * Not be concurrently enrolled on another study involving an investigational agent * Not have any medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only) | Day 1-3 | -Defined as the proportion of donors collecting \>2.0x106 CD34+ cells/kg \[recipient weight\] |
| Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only) | By Day 100 after transplant | -Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria |
| Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only) | Day +21 | -Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Donors Who Experience Infusional Toxicity (Donor Only) | Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm) | -Defined as hypersensitivity reactions. Evaluated by physical exam, blood pressure, heart rate, respirations and temperature one hour prior to the infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours post-infusion |
| Proportion of Recipients Who Experience Chronic GVHD (Recipient Only) | Between Day +100 and +365 post-transplant | -Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria |
| To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity | 0 to 24 hours after dose of IV AMD3100 | -Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion |
| To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax | 0 to 24 hours after dose of IV AMD3100 | -Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion |
| Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only) | 100 days after transplant | -Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause |
| Quality of Life During Stem Cell Mobilization (Recipients Only) | 48-72 hours after last dose of AMD3100 | — |
Countries
United States
Participant flow
Recruitment details
The study was opened to participant enrollment on 05/14/2004 and closed to participant enrollment on 01/26/2009.
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous (SC) Treatment Plan - Donor * Day 1: Mobilization with 240 mcg/kg SC AMD3100 and leukopheresis
* If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3. | 25 |
| Recipients * Conditioning Regimen
* Cyclophosphamide 60mg/kg/day on Days -3 and -2
* TBI 550cGy on Day -1
* GVHD prophylaxis
\*Cyclosporin 3.0mg/kg/day beginning on Day -1 then tapered through Day +100
* PBSC transplant on Day 0 | 46 |
| Intravenous (IV) Treatment Plan - Donor * Day -3: Mobilization with 80-480 mcg/kg/day IV AMD3100 and PK analysis
* Day 1: Mobilization with 240 mcg/kg/day SC AMD3100 and leukopheresis
* If PBSC collected are not adequate, then donor will again be mobilized with AMD3100 and have leukopheresis collection on day 3. | 21 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Determined to be not ineligible | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Subcutaneous (SC) Treatment Plan - Donor | Recipients | Intravenous (IV) Treatment Plan - Donor |
|---|---|---|---|---|
| Age, Continuous | 52 years | 54 years | 53 years | 51 years |
| Region of Enrollment United States | 92 participants | 25 participants | 46 participants | 21 participants |
| Sex: Female, Male Female | 39 Participants | 5 Participants | 26 Participants | 8 Participants |
| Sex: Female, Male Male | 53 Participants | 20 Participants | 20 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 46 / 46 | 46 / 46 |
| serious Total, serious adverse events | 2 / 46 | 12 / 46 |
Outcome results
Primary
Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only)
-Defined as the proportion of donors collecting \>2.0x106 CD34+ cells/kg \[recipient weight\]
Time frame: Day 1-3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous (SC) Treatment Plan - Donor | Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only) | 22 Participants |
| Intravenous (IV) Treatment Plan - Donor | Proportion of Donors From Whom a Sufficient Number of Cells for Transplantation Are Collected in no More Than 2 LP Procedures Following Mobilization With AMD3100 (Donor Only) | 19 Participants |
Primary
Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only)
-Incidence and severity of acute GVHD (aGVHD) will be assessed based on the Seattle criteria
Time frame: By Day 100 after transplant
Population: Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients | Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only) | 15 Participants |
Primary
Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only)
-Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir
Time frame: Day +21
Population: Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients | Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only) | 37 Participants |
Secondary
Proportion of Donors Who Experience Infusional Toxicity (Donor Only)
-Defined as hypersensitivity reactions. Evaluated by physical exam, blood pressure, heart rate, respirations and temperature one hour prior to the infusion and then 15 minutes, 30 minutes, one hour, 2 hours, and 4 hours post-infusion
Time frame: Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous (SC) Treatment Plan - Donor | Proportion of Donors Who Experience Infusional Toxicity (Donor Only) | 0 Participants |
| Intravenous (IV) Treatment Plan - Donor | Proportion of Donors Who Experience Infusional Toxicity (Donor Only) | 0 Participants |
Secondary
Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)
-Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria
Time frame: Between Day +100 and +365 post-transplant
Population: Only 28 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, receiving non-AMD3100 mobilized cells, or death before day +100.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients | Proportion of Recipients Who Experience Chronic GVHD (Recipient Only) | 10 Participants |
Secondary
Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only)
-Death that results from a transplant procedure related complication (e.g. infection, organ failure, hemorrhage, GVHD) rather than from relapse of the underlying disease or an unrelated cause
Time frame: 100 days after transplant
Population: Only 38 recipients received stem cell products on study. The others were not eligible due to relapse/progression, poor donor collection, or receiving non-AMD3100 mobilized cells.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Recipients | Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only) | 2 Participants |
Secondary
Quality of Life During Stem Cell Mobilization (Recipients Only)
Time frame: 48-72 hours after last dose of AMD3100
Population: -Quality of life questionnaires were not collected from the recipients.
Secondary
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax
-Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion
Time frame: 0 to 24 hours after dose of IV AMD3100
Population: Pharmacokinetics were not performed on 2 patients who were considered replacement patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous (IV) Treatment Plan - Donor | To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax | 1058 ng/ml |
Secondary
To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity
-Blood for pharmacokinetics were drawn prior to infusion, 15 minutes after infusion, 30 minutes after infusion, 45 minutes after infusion, 1 hour after infusion, 2 hours after infusion, 4 hours after infusion, 6 hours after infusions, and 24 hours after infusion
Time frame: 0 to 24 hours after dose of IV AMD3100
Population: Pharmacokinetics were not performed on 2 patients who were considered replacement patients.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Intravenous (IV) Treatment Plan - Donor | To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity | 5150 ng*hr/mL |