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Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

ConditionsAcute Biphenotypic LeukemiaAcute LeukemiaAcute Leukemia of Ambiguous LineageAcute Lymphoblastic LeukemiaAcute Undifferentiated LeukemiaAllogeneic Hematopoietic Stem Cell Transplantation RecipientBlastic Plasmacytoid Dendritic Cell NeoplasmBlasts Under 25 Percent of Bone Marrow Nucleated CellsBlasts Under 5 Percent of Bone Marrow Nucleated CellsMixed Phenotype Acute LeukemiaMyelodysplastic Syndrome With Excess Blasts-1Myelodysplastic Syndrome/Acute Myeloid LeukemiaBurkitt LeukemiaChronic Monocytic LeukemiaLymphoblastic LymphomaMast Cell LeukemiaMyeloproliferative Neoplasm
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age6-26
SponsorFred Hutchinson Cancer Center

About this trial

This phase II trial studies how well naive T-cell depletion works in preventing chronic graft-versus-host disease in children and young adults with blood cancers undergoing donor stem cell transplant. Sometimes the transplanted white blood cells from a donor attack the body's normal tissues (called graft versus host disease). Removing a particular type of T cell (naive T cells) from the donor cells before the transplant may stop this from happening.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Acute lymphoblastic leukemia (ALL) with < 5% marrow blasts.

Acute myeloid leukemia (AML) with < 25% marrow blasts.

Other acute leukemia (OAL) or related neoplasm (including but not limited to acute biphenotypic leukemia [ABL], ambiguous lineage [ALAL], mixed phenotype acute leukemia [MPAL], blastic plasmacytoid dendritic cell neoplasm [BPDCN], acute undifferentiated leukemia [AUL], lymphoblastic lymphoma, Burkitt leukemia/lymphoma, mast cell leukemia, chronic monocytic leukemia [CML] with blast crisis or other chronic myeloproliferative neoplasm) with < 5% marrow blasts.

Myelodysplastic syndrome (MDS) with excess blasts (EB-1 and EB-2) and has received cytotoxic induction chemotherapy (excluding small molecule inhibitors and de-methylating agents)

Disqualifiers

Active central nervous system (CNS) disease. A patient may have a history of CNS disease; however, any CNS disease must be cleared by the end of the pre-conditioning evaluation. If CNS disease is identified on the first cerebrospinal fluid (CSF) evaluation within 30 days of the start of the preparative regimen, a repeat CSF evaluation must be performed and show no evidence of disease in order for the patient to be eligible for the protocol.

Patients on other experimental protocols for the prevention of GVHD.

Matched related donor (MRD): > 100 kg are ineligible

Matched unrelated donor (MUD): > 75 kg must be discussed with the protocol principal investigator (PI) prior to enrollment.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Total-Body Irradiation

    Radiation

    Undergo TBI

  • Thiotepa

    Drug

    Given IV

  • Fludarabine

    Drug

    Given IV

  • Cyclophosphamide

    Drug

    Given IV

  • Busulfan

    Drug

    Given IV

  • Allogeneic Bone Marrow Transplantation

    Procedure/Surgery

    Receive unmanipulated T cell replete BM

  • Tacrolimus

    Drug

    Given IV

  • Methotrexate

    Drug

    Given IV

  • Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation

    Procedure/Surgery

    Receive naive T-cell depleted PBSCs

  • Echocardiography

    Procedure/Surgery

    Undergo ECHO

  • Biospecimen Collection

    Procedure/Surgery

    Undergo CSF and blood sample collection

  • Bone Marrow Aspiration

    Procedure/Surgery

    Undergo bone marrow aspiration

  • Bone Marrow Biopsy

    Procedure/Surgery

    Undergo bone marrow biopsy

Treatment groups

68 Participants
are divided into 2 treatment groups
Group A: Arm I (chemotherapy, naive T-cell depleted PBSC)Experimental treatment 12 interventions
Group B: Arm II (chemotherapy, unmanipulated T cell replete BM)Active comparator 12 interventions

Trial outcomes

Primary outcomes

1

Feasibility achievement

Success defined as achievement of cell selection goals for two consecutive Naive T cells (TN)-depleted peripheral blood stem cells (PBSC) hematopoietic cell transplantation (HCTs) at each study site (Feasibility)

Time frame
Up to 2 years
2

Engraftment of neutrophils by day 28 (Feasibility)

Success defined as achievement neutrophil engraftment (absolute neutrophil count \[ANC\] \>= 500/mm\^3) on first day of three consecutive laboratory values obtained on different days.

Time frame
At day 28
3

Current-graft versus host disease (GVHD)-free, relapse-free survival (Randomized Controlled Trial [RCT])

Defined as alive, no relapse after HCT, no current GVHD requiring prednisone, no graft rejection or graft failure. The proportion of subjects meeting the primary endpoint will be described in each arm with 90% confidence intervals (CI) and compared between arms using the chi-square test. A two-sided 10% significance level will be used for this comparison.

Time frame
At 1 year

Secondary outcomes

1

Chronic GVHD (cGVHD) meeting National Institutes of Health (NIH) criteria and requiring prednisone (RCT)

Cumulative incidence curve will be computed for each arm along with a 90% CI at 1 year and 2 years post-HCT. Death and/or relapse prior to occurrence of cGVHD will be considered as competing risks. The cumulative incidence curves will be compared between arms using Gray's test. The maximum severity of cGVHD will also be described in each arm and compared using the chi-squared test.

Time frame
At 1 and 2 years
2

Proportion of subjects alive and off prednisone (or equivalent systemic corticosteroid) for treatment of GVHD (RCT)

Proportions of subjects alive without requiring use of prednisone (or equivalent systemic corticosteroid) for GVHD will be estimated with 90% CI for both arms at time points over 24 months, and compared using the chi-squared test.

Time frame
At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fred Hutchinson Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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