Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

Study Overview
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Brief Summary
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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
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This study will determine if peripheral blood cells collected following AMD3100 mobilization can be used safely for hematopoietic cell transplantation into HLA-matched recipients.

Official Title
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A Phase I/II Study Evaluating the Safety and Efficacy of AMD3100 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies

Conditions
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Leukemia, Myeloid, Acute, Leukemia, Myelogenous, Chronic, Leukemia, Lymphoblastic, Acute, Lymphocytic Leukemia, Chronic, Myelodysplastic Syndromes, Multiple Myeloma, Lymphoma, Non-Hodgkin, Hodgkin Disease

Intervention / Treatment
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* Drug: AMD3100
* Procedure: Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subcutaneous (SC) Treatment Plan - Donor<br>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. | Drug: AMD3100<br> <br> * Other names: Plerixafor;|
| Experimental: Intravenous (IV) Treatment Plan - Donor<br>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. | Drug: AMD3100<br> <br> * Other names: Plerixafor;|
| Other: Recipients<br>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 | Procedure: Stem Cell Transplant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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] | Day 1-3 | 
| 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 | By Day 100 after transplant | 
| Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only) | -Defined as neutrophil count ≥ 500/ul following conditioning regimen induced nadir | Day +21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Recipients Who Experience Chronic GVHD (Recipient Only) | -Incidence and severity of chronic GVHD will be assessed based on the Seattle criteria | Between Day +100 and +365 post-transplant | 
| 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 | 100 days after transplant | 
| Quality of Life During Stem Cell Mobilization (Recipients Only) |  | 48-72 hours after last dose of AMD3100 | 
| 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 | Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm) | 
| 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 | 0 to 24 hours after dose of IV AMD3100 | 
| 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 | 0 to 24 hours after dose of IV AMD3100 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plerixafor, Stem cell transplantation, Stem cells, Mobilization