CD34+ (Malignant) Stem Cell Selection for Patients Receiving Allogenic Stem Cell Transplant

Myelodysplastic Syndrome (MDS) Clinical Trial

Official title:

CD34+ Stem Cell Selection for Patients Receiving a Matched or Partially Matched Family or Unrelated Adult Donor Allogeneic Stem Cell Transplant for Malignant Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02061800
• Other study ID #: AAAK8060
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 3, 2013
• Est. completion date: December 2028

Study information

• Verified date: June 2020
• Source: Columbia University
• Contact: Jody Campbell, MPA
• Email: jc5422[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD.

This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

Description:

Graft versus host disease (GVHD) is one of the serious complications following allogeneic stem cell transplantation. The incidence and severity of GVHD increase with the degree of HLA incompatibility between the host and donor. The most reliable way to prevent acute and chronic GVHD is to remove T cells from the graft. However, the incidence of graft failure increases with the efficiency of T cell depletion and low T cell numbers are predictive of graft failure. Immunomagnetic selection of HLA-mismatched CD34+ progenitor cells has demonstrated high levels of T cell depletion and successful engraftment in adult and pediatric patients with the malignant and nonmalignant disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2028
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

Inclusion Criteria: General Eligibility (All Patients)

• Must be < 22 years of age

• Diagnosed with a malignant disease

• 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

• For unrelated donor: A human leukocyte antigen (HLA) 8/10, 9/10 or 10/10 matched unrelated adult donor (MUD) will be required for study entry

• For 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

• Adequate renal function

• Adequate liver function

• Adequate cardiac function

• Adequate pulmonary function

Exclusion Criteria:

• Patients with documented uncontrolled infection at the time of study entry are not eligible

• Females who are pregnant or breast feeding at the time of study entry are not eligible

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myelogenous Leukemia (AML)
• Chronic Myeloid Leukemia (CML)
• Juvenile Myelomonocytic Leukemia (JMML)
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Juvenile
• Lymphoma
• Lymphoma (Hodgkin's and Non-Hodgkin's)
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Syndrome

Intervention

Device:
• CliniMACS CD34+ Reagent System
The CliniMACS® Reagent System (Miltenyi Biotec, Germany), is a semi-automated immunomagnetic cell selection medical device that is used in vitro to select and enrich specific cell populations in a closed, sterile environment. The system is comprised of a computer controlled medical device containing a permanent magnet, a closed-system sterile tubing set containing columns coated with a ferromagnetic matrix, and a magnetic cell specific labeling reagent.

Drug:
• Thiotepa
Standard of care: Thiotepa should be diluted in normal saline (NS) (1-5 mg/ml) and infused over 2 hrs on Days -5, -4. IV fluids should be at maintenance rate (1500 ml/m2). It is recommended that total parental nutrition not being used during Thiotepa administration as amino acid infusions may interfere with Thiotepa metabolism.
• Cyclophosphamide
Standard of care: Cyclophosphamide (Cytoxan) should be infused over one hour. The drug can be diluted in dextrose water solvent (D5W), NS, or other solutions (250cc) to a maximum concentration of 20 mg/mL.
• Alemtuzumab
Standard of care: Each dose of alemtuzumab is to be diluted in D5W or NS (maximum concentration: 0.3 mg/mL) for IV infusion over two hours.
• Tacrolimus
Standard of care: Tacrolimus dosing will be 0.03mg/kg/24 hours as continuous IV infusion or 0.12 mg/kg/day po divided Q8-12 hr
• Melphalan
Standard of care: Melphalan 45mg/m2 (1.5 mg/kg IV for children <1 year of age or <10 kg) diluted in 0.9% NS to a concentration of 0.1- 0.45mg/ml, given IV over 30 minutes.
• Busulfan
Standard of care: Busulfan will be given IV in 0.9% sodium chloride or D5W to a final solution for infusion equal to 10 times the volume of diluent to Busulfex (to a concentration >0.5 mg/mL), through a central venous access device over 2 hours.
• Fludarabine
Standard of care: Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
• Methylprednisolone
Standard of care: Methylprednisolone will be give IV slow infusion over 15-30 minutes.

Locations

Country	Name	City	State
United States	Columbia University Medical Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Diane George

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of acute GVHD	Acute GVHD will be assessed and graded with standard NCI grading criteria.Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2 years and yearly (366+ days post-transplant)	Up to 2 years post-transplant
Secondary	Time to neutrophil engraftment	Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant. Neutrophil engraftment is defined as the first of three days following the neutrophil nadir with an absolute neutrophil count above 500/mm3.	Up to 1 year post-transplant
Secondary	Time to immune reconstitution	Immune reconstitution studies will be conducted (For T-cell, B-cell, natural killer (NK)-cell and immunoglobulins) 60 days post-transplant, 100 days post-transplant, 150 days post-transplant, 180 days post-transplant, 270 days post-transplant, 1-year post-transplant, and 2 years post transplant.	Up to 2 years post-transplant
Secondary	Incidence of infection complications including bacterial, viral, fungal and atypical mycobacterial and other infections	Will be assessed weekly or more as indicated until 84 or 100 days post-transplant, then as clinically indicated.	Up to 100 days post-transplant
Secondary	Time to platelet engraftment	Will be assessed multiple times while hospitalized, 1-60 days post transplant, 100 days post-transplant, 180 days post-transplant, and 1-year post transplant.	Up to 1 year post-transplant
Secondary	Incidence of chronic GVHD	Chronic GVHD will be assessed and graded with standard NCI grading criteria.	Up to 2 years post-transplant
Secondary	Severity of acute GVHD	Acute GVHD will be assessed and graded with standard NCI grading criteria.	Up to 2 years post-transplant
Secondary	Severity of chronic GVHD	Chronic GVHD will be assessed and graded with standard NCI grading criteria. Evaluated daily while hospitalized, then weekly (1-60 days post-transplant), as clinically indicated (60-365 days post transplant), then 1 year, 1.5 years, 2	Up to 2 years post-transplant
Secondary	Incidence of primary graft failure	Primary graft rejection is defined as the presence of < 20% donor cells	42 (or more) days post-transplant
Secondary	Incidence of secondary graft failure	The presence of < 20% donor derived hematopoietic cells in peripheral blood	42 (or more) days post-transplant