CD34+ Stem Cell Selection in Preventing Graft-Versus-Host Disease in Younger Patients with Malignant Disease Undergoing Donor Stem Cell Transplant

Status: Active

Description

This phase I / II trial studies cluster of differentiation 34 positive (CD34+) stem cell selection in preventing graft-versus-host-disease (GVHD) in younger patients with malignant disease undergoing donor stem cell transplant. Selected CD34+ stem cell may help stop the patient's immune system from rejecting the donor's stem cells and prevent GVHD.

Eligibility Criteria

Inclusion Criteria

  • GENERAL ELIGIBILITY (ALL PATIENTS):
  • Patient or the patient's legally authorized guardian must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects), and must sign an informed consent in accordance with the institutional policies approved by the U.S. Department of Health and Human Services
  • Approval for the use of this treatment protocol by the individual institution’s Human Rights Committee must be obtained, in accordance with the institutional assurance policies of the U.S. Department of Health and Human Services
  • Human leukocyte antigen (HLA) matching: * HLA typing will be performed by high resolution molecular deoxyribonucleic acid (DNA) typing for HLA class 1 A, B and C, and class II DRB1 and DQB1 alleles
  • UNRELATED DONOR: an HLA 7/8 or 8/8 HLA A, B and C (class I) and HLA DRB1 (class II) alleles, or 9/10 or 10/10 HLA A, B and C (class I) and HLA DRB1 and DQB1 (class II) alleles will be required for study entry
  • RELATED DONOR: a 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 matched (or partially matched) family donor will be required for study entry; HLA typing can be performed at any time prior to conditioning and must be performed twice on both donor and recipient
  • ELIGIBILITY FOR MYELOABLATIVE CONDITIONING
  • Serum creatinine < 1.5 x upper limits of normal, or
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 100 ml/min/1.73 m^2
  • Total bilirubin < 1.5 x upper limits of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3.0 x upper limit of normal
  • Shortening fraction > 27% by echocardiogram, or
  • Ejection fraction of > 47% by radionucleotide angiogram or echocardiogram
  • Corrected diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% by pulmonary function test
  • For children who are unable to perform pulmonary function testing, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% on room air
  • ELIGIBILITY FOR REDUCED INTENSITY CONDITIONING:
  • Serum creatinine =< 2.0 x upper limits of normal, or
  • Creatinine clearance or radioisotope GFR >= 60 ml/min/1.73 m^2
  • Total bilirubin < 2.0 x upper limits of normal
  • SGOT (AST) or SGPT (ALT) < 5.0 x upper limit of normal
  • Shortening fraction of > 25% by echocardiogram, or
  • Ejection fraction of > 40% by radionuclide angiogram or echocardiogram
  • Corrected DLCO > 40% by pulmonary function test
  • For children who are unable to perform pulmonary function testing, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 92% in room air
  • ELIGIBILITY FOR CD34 SELECTED STEM CELL INFUSION FOLLOWING PRIOR ALLOGENEIC STEM CELL TRANSPLANT (MAY BE REFERRED TO AS A "BOOST")
  • Requirement for CD34+ stem cell selection for a second infusion of stem cells following an allogeneic stem cell transplant from a related or unrelated adult donor for the following conditions: * Primary graft rejection * Secondary graft rejection * Poor graft function * Disease recurrence Note: pre-infusion conditioning with chemotherapy and/or immunotherapy to be determined by the primary BMT physician and the protocol principal investigator (PI) based on clinical condition of the patient * Specific Organ System Function Requirements from PBMT 1001 ** Myeloablative *** Cardiac (shortening fraction of > 26% by echo or ejection fraction of > 47%) *** Renal (creatinine clearance or glomerular filtration rate [GFR] >= 40 ml/min, or > 60 ml/min.1.73 m^2) *** Pulmonary (DLCO > 50% by pulmonary function test [PFT]) *** Liver (AST/ALT no greater than 3 times the upper limit of normal) ** Reduced Intensity *** Cardiac (shortening fraction of > 20% by echo or ejection fraction of > 40%) *** Renal (creatinine clearance or GFR >= 30 ml/min, or > 40 ml/min 1.73 m^2) *** Pulmonary (DLCO > 40% by PFT) *** Liver (AST/ALT no greater than 5 times the upper limit of normal)
  • Malignant disorders: * Chronic myeloid leukemia (CML) (chronic phase, accelerated phase or blast crisis) * Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), juvenile myelomonocytic leukemia (JMML) * Acute lymphoblastic leukemia (ALL) * Lymphoma (Hodgkin’s and non-Hodgkin’s)
  • DONOR: HLA typing will be performed by high resolution molecular DNA typing for HLA class 1 A, B and C, and class II DRB1 and DQB1 alleles
  • DONOR: All donors will be screened for the following: * Human immunodeficiency virus (HIV) I * HIV II * Hepatitis surface antigen (HbsAg) * Hepatitis B core antibody (HBc) * Hepatitis C virus (HCV) * Cytomegalovirus (CMV) * Syphilis * Human T-lymphotropic virus (HTLV I/II) * Epstein-Barr virus (EBV) and adenovirus immunoglobulin G (IgG) when feasible
  • DONOR: unrelated adult donors must be matched by high resolution molecular DNA typing at 7/8 or 8/8 HLA A, B and C (class I) and HLA DRB1 (class II) alleles, or 9/10 or 10/10 HLA A, B and C (class I) and HLA DRB1 and DQB1(class II) alleles
  • DONOR: unrelated donors will be identified through the National Marrow Donor Program (NMDP) or equivalent donor search organization
  • DONOR: related donors must be matched by high resolution molecular DNA typing at 5/10, 6/10, 7/10, 8/10, 9/10 or 10/10 HLA A, B and C (class I) and HLA class II DRB1 and DQB1 alleles
  • DONOR: related donors must meet eligibility criteria as per BMT Standard Operating Procedures (SOP) 1002
  • DONOR: related donors and unrelated adult donors, who are harvested at Columbia University Medical Center (CUMC), will receive filgrastim (G-CSF) 5-10 ug/kg/d subcutaneously x 4 days (or, if unable to tolerate G-CSF, sargramostim [GM-CSF] 250-500 mcg/m^2/day subcutaneously x 4 days) and then undergo leukapheresis; if necessary, plerixafor may be included for mobilization

Exclusion Criteria

  • Infection: patients with documented uncontrolled infection at the time of study entry are not eligible
  • Pregnancy/breast feeding: females who are pregnant or breast feeding at the time of study entry are not eligible

Locations & Contacts

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Diane Marie George
Phone: 212-305-2466

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine the incidence and severity of acute graft-versus-host disease (GVHD) following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant from a family member or unrelated adult donor for a malignant condition.

II. To quantify the incidence of primary and secondary graft failure following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant for a malignant disease from a family member or adult unrelated donor.

III. To assess event free survival and overall survival following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant for a malignant disease from a family member or adult unrelated donor.

SECONDARY OBJECTIVES:

I. To determine the time to neutrophil and platelet engraftment following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant for a malignant disease from a family member or unrelated adult donor.

II. To determine the time to immune reconstitution (including normalization of T, B and natural killer [NK] cell repertoire and immunoglobulin G production) following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant for a malignant disease from a family member or adult unrelated donor.

III. To establish the incidence of infectious complications including bacterial, viral, fungal, atypical mycobacterial and other infections following CD34+ selection in children, adolescents and young adults receiving an allogeneic peripheral blood stem cell transplant for a non-malignant disease from a family member or adult unrelated donor.

OUTLINE:

Patients receive a full intensity or a reduced intensity pre-transplant conditioning regimens at the discretion of the primary attending physician and the protocol principle investigator. All patients undergo allogeneic CD34+ stem cell selection bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) on day 0. Beginning on day 60, patients who develop < grade II acute GVHD receive tacrolimus taper.

After completion of study treatment, patients are followed up periodically.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center

Principal Investigator
Diane Marie George

Trial IDs

Primary ID AAAK8060
Secondary IDs NCI-2014-00137
Clinicaltrials.gov ID NCT02061800