Back to results

TCR Alpha/Beta and CD19-deplete Haplo-HSCT

Primary Purpose

Pediatric Patients, Hematologic Malignancy, Other Hematologic Condition

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

CliniMACS Plus Instrument

About this trial

This is an interventional treatment trial for Pediatric Patients focused on measuring Donor, granulocyte stimulating factor (GCSF), apheresis

Eligibility Criteria

31 Days - 30 Years (Child, Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Age 31 days to <30 years
Have a malignant or non-malignant hematologic disease, defined as disease resulting from abnormal function of a cell of the hematopoietic stem cell lineage, that could benefit from an allogeneic HCT. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias/marrow failure, white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities.
Clinical remission for patients with acute leukemia (MDS/AML excluded) or lymphoma
Lack a healthy and willing HLA-identical related donor, with the exception of patients with FA who will be eligible with a willing HLA-identical related donor given the standard use of T-cell depletion in matched sibling donor HCT in FA
Have a related or an unrelated donor who meets the donor selection criteria, is healthy, willing, and able to receive GCSF with or without Plerixafor, and undergo apheresis through placement of catheters in the antecubital veins or a temporary central venous catheter
Able to give informed consent if ≥ 18 years, or with legal guardian capable of giving informed consent if < 18 years
Provision of signed and dated informed consent form

Exclusion Criteria:

Uncontrolled, active infection at time of HCT
HIV positivity
Cardiac ejection fraction <45%
Creatinine clearance <60 mL/min/1.72 mL
Pulmonary diffusion capacity (adjusted for hemoglobin), FEV1, or FVC <60% of predicted or an O2 saturation <94% on room air if unable to perform pulmonary function testing
Serum ALT >5x upper limit of normal or bilirubin >2
Performance score (Lansky or Karnofsky) <50
Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.

Sites / Locations

Children's Hospital Colorado

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pediatric patients with malignant or non-malignant hematologic condition

Arm Description

The infusion of the final TCRαβ/CD19 depleted product will be given through the recipient's central venous catheter and will be administered fresh, without cryopreservation whenever possible. If the product must be cryopreserved and then thawed, this will be done according to institutional standards.

Outcomes

Primary Outcome Measures

Incidence of severe (grade III-IV) acute graft-versus-host disease (GVHD) at day 100 after infusion of a TCRαβ+/CD19+ negative, peripheral blood stem cell (PBSC) product without additional GVHD prophylaxis.

Grade to be determined using Acute GVHD Staging Scale

Secondary Outcome Measures

Number of patients with non-engraftment

Defined as the lack of donor-derived neutrophil engraftment

Number of patients with relapse

Interval from transplant to relapse/recurrence of disease

Number of treatment-related mortality (TRM)

Defined as death due to regimen-related toxicity or GVD.

Disease-free Survival (DFS) measured in days

Defined as the minimum time interval from transplant to relapse/recurrence of disease, death or last follow-up.

Overall Survival (OS) measured in days

Determined at 1 year post-HCT

Immune Reconstitution

Incidence of absolute CD4+ T-cell count >400 cells at 1 year post-HCT

Post-HCT infections

Incidence of bacterial, fungal, and viral infections at day +100

Full Information

NCT ID

NCT05288595

First Posted

March 10, 2022

Last Updated

March 10, 2023

Sponsor

University of Colorado, Denver

1. Study Identification

Unique Protocol Identification Number

NCT05288595

Brief Title

TCR Alpha/Beta and CD19-deplete Haplo-HSCT

Official Title

TCR Alpha/Beta and CD19-depleted Allogeneic Hematopoietic Cell Transplant for Malignant and Non-Malignant Disease

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

December 2023 (Anticipated)

Primary Completion Date

April 2026 (Anticipated)

Study Completion Date

April 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Device Product Not Approved or Cleared by U.S. FDA

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is an open label, interventional, non-randomized, phase II trial of TCR alpha/beta and CD19-depeleted allogeneic HCT in pediatric patients with hematologic disease.

Detailed Description

This is a single-site, open label, interventional, non-randomized, phase II trial of TCRαβ/CD19 deplete allogeneic HCT as donor source and sole GVHD prophylaxis in pediatric patients with either malignant or non-malignant hematologic disease who are eligable for allogeneic HCT, but lack a HLA-matched sibling donor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pediatric Patients, Hematologic Malignancy, Other Hematologic Condition

Keywords

Donor, granulocyte stimulating factor (GCSF), apheresis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Eligible Patients with a hematologic disease who could benefit from HCT with an eligible mismatched related or unrelated donor per donor selection criteria. Patient/recipient admitted of HCT/start of preparative regimen and stem cell infusion

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pediatric patients with malignant or non-malignant hematologic condition

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

CliniMACS Plus Instrument

Intervention Description

Miltenyi Biotec's CliniMACS Plus Instrument is to be used to TCRαβ CD19 deplete products utilized in this protocol. The CliniMACS Plus is an automated cell separation platform which is functionally closed, maintaining a sterile system for cell depletion and enrichment utilizing a magnetic separation column. Reagents and supplies are to be used for research only but are manufactured and tested under a quality system certified to ISO 13485. Should CD34 selection be required to augment stem cell dose, Miltenyi Biotec's CliniMACS® Plus CD34 Reagent System is FDA approved as a Humanitarian Use Device (HUD). The approved indication was the treatment of patients with acute myeloid leukemia (AML) undergoing myeloablative transplant from matched related allogeneic donors. The CliniMACS® Plus reagent system was approved to obtain an enriched CD34+ cell population for hematopoietic reconstitution without the need for GVHD prophylaxis.

Primary Outcome Measure Information:

Title

Description

Grade to be determined using Acute GVHD Staging Scale

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Number of patients with non-engraftment

Description

Defined as the lack of donor-derived neutrophil engraftment

Time Frame

100 days

Title

Number of patients with relapse

Description

Interval from transplant to relapse/recurrence of disease

Time Frame

1 year

Title

Number of treatment-related mortality (TRM)

Description

Defined as death due to regimen-related toxicity or GVD.

Time Frame

1 year

Title

Disease-free Survival (DFS) measured in days

Description

Defined as the minimum time interval from transplant to relapse/recurrence of disease, death or last follow-up.

Time Frame

1 year

Title

Overall Survival (OS) measured in days

Description

Determined at 1 year post-HCT

Time Frame

1 year

Title

Immune Reconstitution

Description

Incidence of absolute CD4+ T-cell count >400 cells at 1 year post-HCT

Time Frame

1 year

Title

Post-HCT infections

Description

Incidence of bacterial, fungal, and viral infections at day +100

Time Frame

100 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

31 Days

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 31 days to <30 years Have a malignant or non-malignant hematologic disease, defined as disease resulting from abnormal function of a cell of the hematopoietic stem cell lineage, that could benefit from an allogeneic HCT. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias/marrow failure, white blood cell abnormalities, red blood cell abnormalities, and platelet abnormalities. Clinical remission for patients with acute leukemia (MDS/AML excluded) or lymphoma Lack a healthy and willing HLA-identical related donor, with the exception of patients with FA who will be eligible with a willing HLA-identical related donor given the standard use of T-cell depletion in matched sibling donor HCT in FA Have a related or an unrelated donor who meets the donor selection criteria, is healthy, willing, and able to receive GCSF with or without Plerixafor, and undergo apheresis through placement of catheters in the antecubital veins or a temporary central venous catheter Able to give informed consent if ≥ 18 years, or with legal guardian capable of giving informed consent if < 18 years Provision of signed and dated informed consent form Exclusion Criteria: Uncontrolled, active infection at time of HCT HIV positivity Cardiac ejection fraction <45% Creatinine clearance <60 mL/min/1.72 mL Pulmonary diffusion capacity (adjusted for hemoglobin), FEV1, or FVC <60% of predicted or an O2 saturation <94% on room air if unable to perform pulmonary function testing Serum ALT >5x upper limit of normal or bilirubin >2 Performance score (Lansky or Karnofsky) <50 Pregnant or lactating females, as many medications necessary for a successful HCT are potentially harmful to unborn babies and infants.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Kayla Pacheco

Phone

17207774151

kayla.pacheco@childrenscolorado.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alisa B Lee Sherick

Organizational Affiliation

University of Colorado, Denver

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Hospital Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Kayla Pacheco

Phone

720-777-4151

kayla.pacheco@childrenscolorado.org

First Name & Middle Initial & Last Name & Degree

Alisa Lee Sherick

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

TCR Alpha/Beta and CD19-deplete Haplo-HSCT

We'll reach out to this number within 24 hrs