RECRUITING

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

Conditions

Acute Biphenotypic Leukemia Acute Leukemia Acute Leukemia of Ambiguous Lineage Acute Lymphoblastic Leukemia Acute Undifferentiated Leukemia Allogeneic Hematopoietic Stem Cell Transplantation Recipient Blastic Plasmacytoid Dendritic Cell Neoplasm Blasts Under 25 Percent of Bone Marrow Nucleated Cells Blasts Under 5 Percent of Bone Marrow Nucleated Cells Mixed Phenotype Acute Leukemia Myelodysplastic Syndrome With Excess Blasts-1 Myelodysplastic Syndrome/Acute Myeloid Leukemia Burkitt Leukemia Chronic Monocytic Leukemia Lymphoblastic Lymphoma Mast Cell Leukemia Myeloproliferative Neoplasm

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Multi-Center Phase II Randomized Controlled Trial of Naïve T Cell Depletion for Prevention of Chronic Graft-Versus-Host Disease in Children and Young Adults

Quick Facts

Study Start:2019-08-29

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03779854

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:6 Months to 26 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* The patient must have one of the following diagnoses and be considered to be an appropriate candidate for allogeneic HCT by the study site principal investigator (PI): * 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) * Age 6 months to 26 years at the time informed consent is obtained using the Informed Consent to Participate in a Research Study form * Matched related donor (MRD) or matched unrelated donor (MUD) (defined as 8/8 match for human leukocyte antigen \[HLA\]-A, -B, -C, -DRB1). * Planned product type for infusion is PBSC or BM (i.e. not cord blood): * For feasibility phase, planned product type for infusion must be PBSC. * For RCT, planned product type must be PBSC or BM. * Karnofsky or Lansky score \>= 60%. * Left ventricular ejection fraction (LVEF) at rest \>= 40%. * Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin) \>= 60% predicted by pulmonary function tests (PFTs) * Total bilirubin =\< 2 x upper limit of normal (ULN) (unless value\[s\] \> 2 x ULN are disease- or medication-related). * Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 2 x ULN (unless value\[s\] \> 2 x ULN are disease- or medication-related). * Serum creatinine (SCr) within normal range for age. If SCr is outside normal range for age, creatinine clearance (CrCl) \> 40 mL/min/1.73m\^2 must be obtained (measured by 24-hour \[hr\] urine specimen or nuclear glomerular filtration rate \[GFR\]). * Age (Years): Maximum SCr (mg/dL) * =\< 5: 0.8 * 6-10: 1 * 11-15: 1.2 * \> 15: 1.5 * Recipient informed consent/assent/legal guardian permission documentation must be obtained. * DONOR: May be related (MRD) or unrelated (MUD) to the subject. * DONOR: Must be matched to the subject at 8/8 HLA alleles (HLA-A, -B, -C, and -DRB1) * DONOR: Be \>=14 years of age. * DONOR: Must be available to donate in the United States of America (USA) (i.e. excludes international donors). * DONOR: Must agree to donate BM or PBSC (i.e. agree to donate whichever product type is requested) (applicable only to the RCT phase of this study). * DONOR: MUDs: * Must give informed consent according to applicable National Marrow Donor Program (NMDP) donor regulatory requirements * Must meet eligibility criteria as defined by the NMDP or be ineligible with statement of urgent medical need (exception 21 CFR 1271.65(b)(iii)) * Tests must be performed using Food and Drug Administration (FDA) licensed, cleared, and approved test kits in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory * DONOR: MRDs: * Must be negative for human immunodeficiency virus (HIV)-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2, hepatitis B, hepatitis C (serological and/or nucleic acid testing \[NAT\] and/or other approved testing) * Must meet institutional donor eligibility criteria, or be ineligible with statement that the donor is a first or second degree relative (exception 21 CRF 1271.65(b)(i)). * Tests must be performed using FDA licensed, cleared, and approved test kits in a CLIA-certified laboratory.	* 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. * Patient body weight: * 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. * HIV-positive. * Uncontrolled infections must be evaluated by an infectious disease physician and considered suitable to undergo HCT by the study site PI, infectious disease physician and protocol PI. Upper respiratory tract infection (URI) does not constitute an uncontrolled infection in this context. * Life expectancy \< 3 months from disease other than acute leukemia or myelodysplastic syndrome (MDS). * Significant medical condition that would make recipient unsuitable for HCT. * Prior allogeneic or autologous HCT. * Females who are pregnant or breastfeeding. * Patients of child bearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during study treatment and for 12 months following HCT. * Known hypersensitivity to tacrolimus, fludarabine, or methotrexate (MTX).

Inclusion Criteria

Exclusion Criteria

* The patient must have one of the following diagnoses and be considered to be an appropriate candidate for allogeneic HCT by the study site principal investigator (PI):
* 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)
* Age 6 months to 26 years at the time informed consent is obtained using the Informed Consent to Participate in a Research Study form
* Matched related donor (MRD) or matched unrelated donor (MUD) (defined as 8/8 match for human leukocyte antigen \[HLA\]-A, -B, -C, -DRB1).
* Planned product type for infusion is PBSC or BM (i.e. not cord blood):
* For feasibility phase, planned product type for infusion must be PBSC.
* For RCT, planned product type must be PBSC or BM.
* Karnofsky or Lansky score \>= 60%.
* Left ventricular ejection fraction (LVEF) at rest \>= 40%.
* Diffusing capacity of the lungs for carbon monoxide (DLCO) (corrected for hemoglobin) \>= 60% predicted by pulmonary function tests (PFTs)
* Total bilirubin =\< 2 x upper limit of normal (ULN) (unless value\[s\] \> 2 x ULN are disease- or medication-related).
* Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =\< 2 x ULN (unless value\[s\] \> 2 x ULN are disease- or medication-related).
* Serum creatinine (SCr) within normal range for age. If SCr is outside normal range for age, creatinine clearance (CrCl) \> 40 mL/min/1.73m\^2 must be obtained (measured by 24-hour \[hr\] urine specimen or nuclear glomerular filtration rate \[GFR\]).
* Age (Years): Maximum SCr (mg/dL)
* =\< 5: 0.8
* 6-10: 1
* 11-15: 1.2
* \> 15: 1.5
* Recipient informed consent/assent/legal guardian permission documentation must be obtained.
* DONOR: May be related (MRD) or unrelated (MUD) to the subject.
* DONOR: Must be matched to the subject at 8/8 HLA alleles (HLA-A, -B, -C, and -DRB1)
* DONOR: Be \>=14 years of age.
* DONOR: Must be available to donate in the United States of America (USA) (i.e. excludes international donors).
* DONOR: Must agree to donate BM or PBSC (i.e. agree to donate whichever product type is requested) (applicable only to the RCT phase of this study).
* DONOR: MUDs:
* Must give informed consent according to applicable National Marrow Donor Program (NMDP) donor regulatory requirements
* Must meet eligibility criteria as defined by the NMDP or be ineligible with statement of urgent medical need (exception 21 CFR 1271.65(b)(iii))
* Tests must be performed using Food and Drug Administration (FDA) licensed, cleared, and approved test kits in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
* DONOR: MRDs:
* Must be negative for human immunodeficiency virus (HIV)-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2, hepatitis B, hepatitis C (serological and/or nucleic acid testing \[NAT\] and/or other approved testing)
* Must meet institutional donor eligibility criteria, or be ineligible with statement that the donor is a first or second degree relative (exception 21 CRF 1271.65(b)(i)).
* Tests must be performed using FDA licensed, cleared, and approved test kits in a CLIA-certified laboratory.

* 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.
* Patient body weight:
* 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.
* HIV-positive.
* Uncontrolled infections must be evaluated by an infectious disease physician and considered suitable to undergo HCT by the study site PI, infectious disease physician and protocol PI. Upper respiratory tract infection (URI) does not constitute an uncontrolled infection in this context.
* Life expectancy \< 3 months from disease other than acute leukemia or myelodysplastic syndrome (MDS).
* Significant medical condition that would make recipient unsuitable for HCT.
* Prior allogeneic or autologous HCT.
* Females who are pregnant or breastfeeding.
* Patients of child bearing age who are presumed to be fertile and are unwilling to use an effective birth control method or refrain from sexual intercourse during study treatment and for 12 months following HCT.
* Known hypersensitivity to tacrolimus, fludarabine, or methotrexate (MTX).

Contacts and Locations

Study Contact

Marie Bleakley

CONTACT

206-667-6572

mbleakle@fredhutch.org

Principal Investigator

Marie Bleakley

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Children's Hospital of Los Angeles

Los Angeles, California, 90027

United States

Children's National Medical Center

Washington, District of Columbia, 200100

United States

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329

United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242

United States

Dana Farber / Boston Children's Hospital

Boston, Massachusetts, 02115

United States

UH Rainbow Babies and Children's Hospital (University Hospitals Cleveland Medical Center)

Cleveland, Ohio, 44106

United States

Cleveland Clinic Foundation

Cleveland, Ohio, 44195

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224

United States

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Marie Bleakley, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-08-29

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2019-08-29

Study Completion Date2025-12-31

Terms related to this study

Additional Relevant MeSH Terms

Acute Biphenotypic Leukemia
Acute Leukemia
Acute Leukemia of Ambiguous Lineage
Acute Lymphoblastic Leukemia
Acute Undifferentiated Leukemia
Allogeneic Hematopoietic Stem Cell Transplantation Recipient
Blastic Plasmacytoid Dendritic Cell Neoplasm
Blasts Under 25 Percent of Bone Marrow Nucleated Cells
Blasts Under 5 Percent of Bone Marrow Nucleated Cells
Mixed Phenotype Acute Leukemia
Myelodysplastic Syndrome With Excess Blasts-1
Myelodysplastic Syndrome/Acute Myeloid Leukemia
Burkitt Leukemia
Chronic Monocytic Leukemia
Lymphoblastic Lymphoma
Mast Cell Leukemia
Myeloproliferative Neoplasm