Clinical trial NCT00241358: Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia, Myeloid, Acute
Leukemia, Myelogenous, Chronic
Leukemia, Lymphoblastic, Acute
Lymphocytic Leukemia, Chronic
Myelodysplastic Syndromes
Multiple Myeloma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Keywords: Plerixafor
Stem cell transplantation
Stem cells
Mobilization
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2005-10-18
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Day 1-3
measure: Proportion of Recipients Who Experience Grade 2-4 Acute GVHD (Recipient Only)
timeFrame: By Day 100 after transplant
measure: Proportion of Recipients Who Successfully Engraft by Day +21 After Transplant (Recipient Only)
timeFrame: Day +21
Secondary outcomes:
measure: Proportion of Recipients Who Experience Chronic GVHD (Recipient Only)
timeFrame: Between Day +100 and +365 post-transplant
measure: Proportion of Recipients Who Experience Mortality Before Day 100 After Transplant (Recipient Only)
timeFrame: 100 days after transplant
measure: Quality of Life During Stem Cell Mobilization (Recipients Only)
timeFrame: 48-72 hours after last dose of AMD3100
measure: Proportion of Donors Who Experience Infusional Toxicity (Donor Only)
timeFrame: Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
measure: To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Cmax
timeFrame: 0 to 24 hours after dose of IV AMD3100
measure: To Determine the Pharmacokinetics of IV AMD3100 (IV Donor Arm Only) as Measured by Mean AUC From Time 0 to Infinity
timeFrame: 0 to 24 hours after dose of IV AMD3100
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: John F. DiPersio, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Devine SM, Vij R, Rettig M, Todt L, McGlauchlen K, Fisher N, Devine H, Link DC, Calandra G, Bridger G, Westervelt P, Dipersio JF. Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction. Blood. 2008 Aug 15;112(4):990-8. doi: 10.1182/blood-2007-12-130179. Epub 2008 Apr 21.
citation: Devine SM, Flomenberg N, Vesole DH, Liesveld J, Weisdorf D, Badel K, Calandra G, DiPersio JF. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol. 2004 Mar 15;22(6):1095-102. doi: 10.1200/JCO.2004.07.131.
citation: Flomenberg N, Devine SM, Dipersio JF, Liesveld JL, McCarty JM, Rowley SD, Vesole DH, Badel K, Calandra G. The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone. Blood. 2005 Sep 1;106(5):1867-74. doi: 10.1182/blood-2005-02-0468. Epub 2005 May 12.
citation: Schroeder MA, Rettig MP, Lopez S, Christ S, Fiala M, Eades W, Mir FA, Shao J, McFarland K, Trinkaus K, Shannon W, Deych E, Yu J, Vij R, Stockerl-Goldstein K, Cashen AF, Uy GL, Abboud CN, Westervelt P, DiPersio JF. Mobilization of allogeneic peripheral blood stem cell donors with intravenous plerixafor mobilizes a unique graft. Blood. 2017 May 11;129(19):2680-2692. doi: 10.1182/blood-2016-09-739722. Epub 2017 Mar 14.