Intravenous (IV) AMD3100 for Mobilization and Matched Related Transplant for Advanced Hematological Malignancies
Information source: Washington University School of Medicine
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hematologic Neoplasms
Intervention: AMD3100 (Drug); Leukopheresis (Procedure)
Phase: Phase 2
Status: Completed
Sponsored by: Washington University School of Medicine Official(s) and/or principal investigator(s): John DiPersio, M.D., Ph.D., Principal Investigator, Affiliation: Washington University School of Medicine
Summary
To reduce the number of donors treated with IV AMD3100 who require a second collection to
obtain the minimum cells necessary for allogeneic stem cell transplant.
Clinical Details
Official title: A Phase II Study Evaluating the Safety and Efficacy of Intravenous AMD3100 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To reduce the number of donors treated with IV AMD3100 who require a second collection to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell transplant when compared to our historic group who received 240ug SC AMD3100.
Secondary outcome: To estimate with 95% confidence intervals the proportion of donors who experience grade 3-4 infusional toxicity & the proportion from whom ≥ 2.0 x 10e6 CD34+ cells/kg recipient weight are safely mobilized following 1 or 2 intravenous infusions.To determine the kinetics of mobilization using IV AMD3100 and to determine if stem cell products collected after mobilization with IV AMD3100 can be used safely for transplant in HLA-matched recipients as measured by neutrophil engraftment by day +21. To determine the pharmacokinetics and pharmacodynamics of IV AMD3100 on stem cell and T-cell phenotyping and on immune reconstitution after transplantation. To determine the rate of acute GVHD and chronic GVHD in patients who receive IV AMD3100 mobilized peripheral blood stem cells. Rate of neutrophil engraftment for recipients Rate of platelet engraftment for recipients Transplant related mortality rate for recipients Grades and rates of grade 3-4 toxicity for recipients
Detailed description:
- To reduce the number of donors treated with IV AMD3100 who require a second collection
to obtain the minimum CD34/kg (2 X 106) necessary for allogeneic stem cell
transplantation when compared to our historic group who received 240ug SC AMD3100 from
33% (8 in 24) to 11% (3 in 27).
- To estimate with 95% confidence intervals the proportion of HLA-identical sibling
donors who experience grade 3-4 infusional toxicity and the proportion from whom ≥ 2. 0
x 10e6 CD34+ cells/kg recipient weight are safely mobilized following one or two
intravenous infusions.
- To determine the kinetics of stem cell and lymphocyte mobilization using IV AMD3100 and
to determine if peripheral blood stem cell products collected after mobilization with
IV AMD3100 can be used safely for hematopoietic cell transplantation in HLA-matched
recipients as measured by neutrophil engraftment by day +21.
- To determine the pharmacokinetics and pharmacodynamics of IV AMD3100 on stem cell and
T-cell phenotyping and on immune reconstitution after transplantation.
- To determine the rate of acute GVHD and chronic GVHD in patients who receive IV AMD3100
mobilized peripheral blood stem cells.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
Donor Eligibility
- Donor is 18 to 70 years of age inclusive.
- If female and of child-bearing age: must be non-pregnant, not breast feeding and
agree to use adequate contraception.
- Donor is a 6/6 HLA-matched sibling willing to donate PBSC 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 calculated 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.
- Donor must be HIV-1&2 antibody and HTLV-I&II antibody sero-negative, by FDA licensed
test.
- Donor must have an ECOG performance status of 0 or 1.
- Donor must demonstrate ability to be compliant with study regimen.
- Donor must not have an active infection at the time of study entry.
- Donor does not have active alcohol or substance abuse within 6 months of study entry.
- Donor is not currently enrolled on another investigational agent study.
- Donor does not have any medical condition, which, in the opinion of the clinical
investigator, would interfere with his/her evaluation.
Recipient Eligibility
- Recipient must have available the successful collection of an AMD3100 mobilized
product. When an adequate collection cannot be obtained using G-CSF, some recipients
may need to receive a combined product of mobilized cells with AMD3100 and G-CSF.
Recipients who receive less than 2. 0 X 106 CD34+ cells/kg/actual recipient weight
after two days of IV AMD3100 will not be considered "eligible" but followed per
protocol for safety purposes only.
- Patient is 18 to 65 years of age inclusive.
- Patient is willing and has a 6/6 HLA-matched sibling willing to donate PBSC for
transplant.
- Patient must provide signed informed consent.
- If female and of child-bearing age: must be non-pregnant, not breast feeding, and
uses adequate contraception.
- Patient must have one of the following diagnoses:
- Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse,
- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse,
- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the
International Prognostic Scoring System,
- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase,
- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater
complete remission, partial remission, or refractory relapse,
- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior
regimens, OR
- Multiple myeloma (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 FEV1 ≥50%
of predicted and a 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 CNS 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 time of transplantation.
- Patient must be HIV-1&2 antibody and HTLV-I & II antibody sero-negative, by FDA
licensed test.
- Patient has an ECOG performance status of 0 or 1.
- Patient must demonstrate ability to be compliant with medical regimen.
- Patient must not have active alcohol or substance abuse within 6 months of study
entry.
- Patient must not be enrolled on another investigational agent concurrently.
- Patient must not have any medical condition, which, in the opinion of the clinical
investigator, would interfere with the evaluation of the patient.
Exclusion Criteria:
- See Inclusion criteria above
Locations and Contacts
Washington University School of Medicine, St. Louis, Missouri 63110, United States
Additional Information
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
Related publications: Lévesque JP, Hendy J, Takamatsu Y, Simmons PJ, Bendall LJ. Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide. J Clin Invest. 2003 Jan;111(2):187-96. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D, Lapidot T. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science. 1999 Feb 5;283(5403):845-8. Broxmeyer HE, Hangoc G, Cooper S, Bridger G. Interference of the SDF-1/CXCR4 axis in mice with AMD3100 induces rapid high level mobilization of hematopoietic progenitor cells, and AMD3100 acts synergistically with G-CSF and MIP-1 alpha to mobilize progenitors. Blood. 2001;96:3371a Broxmeyer HE, Hangoc G, Cooper S, Li X, Bridger G, Clapp DW. AMD3100, an antagonist of CXCR4 and mobilizer of myeloid progenitor cells, is a potent mobilizer of competitive repopulating long term marrow self renewing stem cells in mice. Blood. 2002;98:2397a Liles WC, Broxmeyer HE, Rodger E, Hubel K, Cooper S, Hangoc G, Bridger GJ, Henson GW, Calandra G, Dale D. Leucocytosis and mobilization of pluripotent hematopoietic progenitor cells in healthy volunteers induced by single dose administration of AMD-3100, a CXCR4 antagonist. Blood. 2001;96:3071a Devine S, Adkins D, Khoury H, Vij R, Goodnough LT, Graubert T, Tomasson M, Blum W, DiPersio J, Brown R. Mobilization of donors with GM-CSF plus G-CSF or GM-CSF alone results in significantly different graft composition compared to G-CSF alone. Blood. 2002;100:825a 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. Broxmeyer HE, Orschell CM, Clapp DW, Hangoc G, Cooper S, Plett PA, Liles WC, Li X, Graham-Evans B, Campbell TB, Calandra G, Bridger G, Dale DC, Srour EF. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med. 2005 Apr 18;201(8):1307-18. Hess DA, Bonde J, Craft TP, Wirthlin L, Hohm S, Lahey R, Todt LM, Dipersio JF, Devine SM, Nolta JA. Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor. Biol Blood Marrow Transplant. 2007 Apr;13(4):398-411. Erratum in: Biol Blood Marrow Transplant. 2007 Jun;13(6):747. Craft, Timothy C [corrected to Craft, Timothy P].
Starting date: August 2009
Last updated: July 22, 2013
|