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T-cell Depleted Alternative Donor Transplantation

Primary Purpose

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

CliniMACS® (T cell depletion)

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring T cell depleted, Matched unrelated donors, Haplocompatible donors

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age < 30 years
Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, and immunodeficiencies.
Patients with acute lymphoblastic leukemia must be in morphological remission (< 5% blasts) at the time of transplant. Patients with acute non-lymphocytic leukemia will preferably be in morphologic remission but may be enrolled when aplastic after chemotherapy or with < 20% blasts. Patients with lymphoma must be in complete or close to complete remission (if residual adenopathy, PET scan must be negative or only have slight uptake, eg. SUV < 2).
Patients must lack a healthy HLA-identical related donor of at least one year of age.
Patient must have a mismatched related or an unrelated donor who is:
1. Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
2. Healthy,
3. Willing,
4. For recipients of an unrelated donor transplant, recipient eligibility will be restricted as follows if in the judgment of the recipients' transplant physician, the recipient cannot receive a transplant with combined positive and negative fractions as described in Section 6.1.3.2 or an unmanipulated PBSC product.
5. Meets eligibility criteria for donors.
If only one mismatched related relative is available, an acceptable unrelated donor must be identified as a backup.
Patient or authorized guardian must sign informed consent for this study.

Exclusion Criteria:

Patient with an anticipated life expectancy of < 1 month
Active infectious hepatitis or CMV infection
HIV or HTLV-I/II infection
Serious infection (bacterial, fungal, viral) within the last 4 weeks
Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used.
Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used.
Pulmonary diffusion capacity (adjusted for Hgb), FEV1, or FVC <60% of predicted or O2 sat < 94% if unable to perform PFTs; can be lower if a reduced intensity conditioning regimen is used.
Serum ALT > 3 x upper limit of normal (can be up to 5 x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2. The bilirubin criteria for sickle cell disease patients is direct bilirubin >2x upper limit of normal.
Performance score (Lansky/Karnofsky) < 50
Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.

Sites / Locations

Levine Children's Hospital, Carolinas Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CliniMACS® (T cell depletion)

Arm Description

Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.

Outcomes

Primary Outcome Measures

Number of Participants With Severe Graft vs. Host Disease (GVHD).

Severe GVHD defined as grade III/IV GVHD.

Secondary Outcome Measures

Number of Participants With Engraftment and Time to Engraftment

Engraftment was measured as time to absolute neutrophil count >500

Number of Participants With Post-transplant Infections

Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)

Number of Participants With Post-transplant Leukemia Relapse

Number of Participants With Transplant-related Mortality

Transplant-related mortality includes death due to regimen-related toxicity or GVHD (all causes other than disease relapse). Those who died due to disease relapse are not included in the analyzed population for that time point.

Number of Participants With Transplant-related Toxicities

Overall Survival

Device Performance: Dose of CD34+ Cells and CD3+ Cells Given

For mismatched related donors, the target cell dose after processing is >/= 20 x 10^6 CD34+ cells/kg patient body weight, but >/= 8 x 10^6 is acceptable. For unrelated donors the target cell dose after processing is >/= 10 x 10^6 CD34+ cells/kg patient body weight, but >/= 4 x 10^6 is acceptable. The target T cell dose is </= 3 x 10^4 CD3+ cells/ kg.

Full Information

NCT ID

NCT00968864

First Posted

August 28, 2009

Last Updated

April 20, 2022

Sponsor

Wake Forest University Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT00968864

Brief Title

T-cell Depleted Alternative Donor Transplantation

Official Title

A Phase II Study Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Terminated

Why Stopped

Sponsor/ PI leaving institution, no plans to continue this research at this time

Study Start Date

August 2009 (undefined)

Primary Completion Date

November 2016 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections. Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.

Detailed Description

A major issue in alternative donor (mismatched related and unrelated donor transplantation is the development of graft-versus-host disease (GVHD). Several clinical trials have shown that the use of T-cell depleted peripheral blood stem cells (PBSC) reduces GVHD in alternative donor transplants. The purpose of this study is to determine the ability of CD34 positive selection and T cell depletion using the CliniMACS® Device as the only GVHD prophylaxis to prevent severe acute GVHD in recipients of an alternative donor PBSC transplant. Mismatched related donors will match at least 3 of 6 Human leukocyte antigens(HLA)(haplocompatible) and unrelated donors will match at least 6 out of 8 HLA antigens with the transplant recipient. The conditioning therapy including chemotherapy, anti-thymocyte globulin (ATG), +/- total body irradiation (TBI) will be based on the patient's diagnosis. The transplant recipient will be followed for 5 years after transplant for GVHD, engraftment, post-transplant infections, disease relapse, and overall survival. In addition, this study will serve as a platform for a companion study of therapy to accelerate immune recovery after transplant.

6. Conditions and Keywords

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

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myeloid Leukemia, Myelodysplastic Syndrome, Lymphomas, Bone Marrow Failure, Hemoglobinopathy, Immune Deficiency, Osteopetrosis

Keywords

T cell depleted, Matched unrelated donors, Haplocompatible donors

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

53 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CliniMACS® (T cell depletion)

Arm Type

Experimental

Arm Description

Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.

Intervention Type

Device

Intervention Name(s)

CliniMACS® (T cell depletion)

Other Intervention Name(s)

CliniMACS device, T-cell depletion

Intervention Description

Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.

Primary Outcome Measure Information:

Title

Number of Participants With Severe Graft vs. Host Disease (GVHD).

Description

Severe GVHD defined as grade III/IV GVHD.

Time Frame

Within 30 days after stem cell transplant

Secondary Outcome Measure Information:

Title

Number of Participants With Engraftment and Time to Engraftment

Description

Engraftment was measured as time to absolute neutrophil count >500

Time Frame

Within 28 days after stem cell transplant

Title

Number of Participants With Post-transplant Infections

Time Frame

1 year

Title

Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)

Time Frame

5 years

Title

Number of Participants With Post-transplant Leukemia Relapse

Time Frame

5 years

Title

Number of Participants With Transplant-related Mortality

Description

Time Frame

2 year

Title

Number of Participants With Transplant-related Toxicities

Time Frame

1 year

Title

Overall Survival

Time Frame

2 years

Title

Device Performance: Dose of CD34+ Cells and CD3+ Cells Given

Description

Time Frame

Length of the trial (5 years)

10. Eligibility

Sex

All

Maximum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age < 30 years Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, and immunodeficiencies. Patients with acute lymphoblastic leukemia must be in morphological remission (< 5% blasts) at the time of transplant. Patients with acute non-lymphocytic leukemia will preferably be in morphologic remission but may be enrolled when aplastic after chemotherapy or with < 20% blasts. Patients with lymphoma must be in complete or close to complete remission (if residual adenopathy, PET scan must be negative or only have slight uptake, eg. SUV < 2). Patients must lack a healthy HLA-identical related donor of at least one year of age. Patient must have a mismatched related or an unrelated donor who is: Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter, Healthy, Willing, For recipients of an unrelated donor transplant, recipient eligibility will be restricted as follows if in the judgment of the recipients' transplant physician, the recipient cannot receive a transplant with combined positive and negative fractions as described in Section 6.1.3.2 or an unmanipulated PBSC product. Meets eligibility criteria for donors. If only one mismatched related relative is available, an acceptable unrelated donor must be identified as a backup. Patient or authorized guardian must sign informed consent for this study. Exclusion Criteria: Patient with an anticipated life expectancy of < 1 month Active infectious hepatitis or CMV infection HIV or HTLV-I/II infection Serious infection (bacterial, fungal, viral) within the last 4 weeks Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used. Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used. Pulmonary diffusion capacity (adjusted for Hgb), FEV1, or FVC <60% of predicted or O2 sat < 94% if unable to perform PFTs; can be lower if a reduced intensity conditioning regimen is used. Serum ALT > 3 x upper limit of normal (can be up to 5 x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2. The bilirubin criteria for sickle cell disease patients is direct bilirubin >2x upper limit of normal. Performance score (Lansky/Karnofsky) < 50 Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew Gilman, MD

Organizational Affiliation

Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System

Official's Role

Principal Investigator

Facility Information:

Facility Name

Levine Children's Hospital, Carolinas Medical Center

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29296761

Citation

Gilman AL, Eckrich MJ, Epstein S, Barnhart C, Cannon M, Fukes T, Hyland M, Shah K, Grochowski D, Champion E, Ivanova A. Alternative donor hematopoietic stem cell transplantation for sickle cell disease. Blood Adv. 2017 Jun 28;1(16):1215-1223. doi: 10.1182/bloodadvances.2017005462. eCollection 2017 Jul 11.

Results Reference

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T-cell Depleted Alternative Donor Transplantation

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