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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00241358
• Other study ID #: 03-0349
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 17, 2005
• Last updated: June 5, 2017
• Start date: May 2004
• Est. completion date: February 2010

Study information

• Verified date: June 2017
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: February 2010
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hodgkin Disease
• Leukemia
• Leukemia, Lymphoblastic, Acute
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphocytic Leukemia, Chronic
• Lymphoma, Non-Hodgkin
• Multiple Myeloma
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia

Intervention

Drug:
• AMD3100

Procedure:
• Stem Cell Transplant

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. Epub 2005 May 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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]	Day 1-3
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	By Day 100 after transplant
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	Day +21
Secondary	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
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	100 days after transplant
Secondary	Quality of Life During Stem Cell Mobilization (Recipients Only)		48-72 hours after last dose of AMD3100
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	Day +1 to +3 (SC donor arm) and Day -3 to +3 (IV donor arm)
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	0 to 24 hours after dose of IV AMD3100
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	0 to 24 hours after dose of IV AMD3100

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine