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Acute Biphenotypic LeukemiaPhase 2NCT03779854

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

A Phase 2 study testing Total-Body Irradiation, Thiotepa and Fludarabine in people with Acute Biphenotypic Leukemia and Acute Leukemia, run by Fred Hutchinson Cancer Center at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 6 months to 26 yearsHealthy volunteers can take part
What is being tested?
Total-Body Irradiation, Thiotepa and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
9 sitesUnited States
Study dates
29 Aug 2019to 31 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 26 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • 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
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  • 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)
  • Patients who are unable to perform PFTs (age < 6 years or considered developmentally incapable of PFTs): oxygen saturation (by oximetry) must be >= 92% on room air.
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless value[s] > 2 x ULN are disease- or medication-related).
  • If value(s) are > 2 x ULN and not disease- or medication related, patient must be evaluated by a gastrointestinal (GI) physician. If GI physician considers protocol treatment to be contraindicated for the patient, the patient will not be eligible for the study.
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =< 2 x ULN (unless value[s] > 2 x ULN are disease- or medication-related).
  • If value(s) are > 2 x ULN and not disease- or medication related, patient must be evaluated by a gastrointestinal GI physician. If GI physician considers protocol treatment to be contraindicated for the patient, the patient will not be eligible for the study.
  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30329

  • Dana Farber / Boston Children's Hospital

    Boston, Massachusetts, 02115

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

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the detailed description

Patients are randomized to 1 of 2 arms. All patients receive 1 of 3 conditioning regimens.

CONDITIONING REGIMEN A: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, then receive thiotepa intravenously (IV) over 3 hours once daily (QD) on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2.

CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2.

CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1.

ARM I: Patients receive naive T-cell depleted PBSCs on day 0.

ARM II: Patients receive unmanipulated T cell-replete BM on day 0.

GVHD PROPHYLAXIS: All patients receive tacrolimus IV on days -1 to +50 followed by a taper in the absence of grade II-IV aGVHD. Patients also receive methotrexate IV on days +1, +3, +6, and +11.

Additionally, all patients undergo echocardiography (ECHO) and cerebrospinal fluid (CSF) collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.

After completion of study treatment, patients are followed up at days 28, 56, 90, 180, 270, and 365 and then at months 15, 18, 21, and 24.

Medical subject headings
Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Blastic Plasmacytoid Dendritic Cell Neoplasm, GATA2 Deficiency, Burkitt Lymphoma, Leukemia, Myeloid, Leukemia, Mast-Cell, Myeloproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Total-Body IrradiationRadiation

    Also called Total Body Irradiation, Whole-Body Irradiation, SCT_TBI, TBI

    Undergo TBI

  • ThiotepaDrug

    Also called 1,1',1"-phosphinothioylidynetrisaziridine, Oncotiotepa, STEPA, Tepadina

    Given IV

  • FludarabineDrug

    Also called 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, Fluradosa

    Given IV

  • CyclophosphamideDrug

    Also called Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal

    Given IV

  • BusulfanDrug

    Also called Bussulfam, Busulfanum, Busulfex, Busulphan

    Given IV

  • Allogeneic Bone Marrow TransplantationProcedure or surgery

    Also called Allo BMT, Allogeneic Blood and Marrow Transplantation, Allogeneic BMT

    Receive unmanipulated T cell replete BM

  • TacrolimusDrug

    Also called Fujimycin, Hecoria, Prograf, Protopic

    Given IV

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IV

  • Naive T Cell-Depleted Hematopoietic Stem Cell TransplantationProcedure or surgery

    Receive naive T-cell depleted PBSCs

  • EchocardiographyProcedure or surgery

    Also called EC, ECHO

    Undergo ECHO

  • Biospecimen CollectionProcedure or surgery

    Undergo CSF and blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Undergo bone marrow biopsy

Study groups in NCT03779854
Study groupRoleWhat they receive
Arm I (chemotherapy, naive T-cell depleted PBSC)ExperimentalCONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2. CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2. CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1. TRANSPLANT: Patients receive naive T-cell depleted PBSCs on day 0. GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Additionally, patients undergo ECHO and CSF collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.
Receives: Radiation: Total-Body Irradiation; Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Busulfan; Drug: Tacrolimus; Drug: Methotrexate; Procedure: Naive T Cell-Depleted Hematopoietic Stem Cell Transplantation; Procedure: Echocardiography; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy
Arm II (chemotherapy, unmanipulated T cell replete BM)Active comparatorCONDITIONING REGIMEN A: Patients undergo TBI BID on days -10 to -7, then receive thiotepa IV over 3 hours QD on days -6 and -5, and fludarabine IV over 30 minutes once daily on days -6 to -2. CONDITIONING REGIMEN B: Patients undergo TBI BID on days -8 to -5, then receive fludarabine IV over 30 minutes QD on days -4 to -2, and cyclophosphamide IV over 1 hour QD on days -3 and -2. CONDITIONING REGIMEN C: Patients receive fludarabine IV over 30 minutes QD on days -6 to -2, busulfan IV over 180 minutes QD on days -5 to -2, and undergo total body irradiation BID on day -1. TRANSPLANT: Patients receive unmanipulated T cell-replete BM on day 0. GVHD PROPHYLAXIS: All patients receive tacrolimus IV beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Additionally, patients undergo ECHO and CSF collection at baseline as well as blood sample collection and bone marrow aspiration with or without biopsy throughout the trial.
Receives: Radiation: Total-Body Irradiation; Drug: Thiotepa; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Busulfan; Procedure: Allogeneic Bone Marrow Transplantation; Drug: Tacrolimus; Drug: Methotrexate; Procedure: Echocardiography; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    Measured: 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.

    Measured: 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.

    Measured: At 1 year

Secondary outcomes (2)

  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.

    Measured: 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.

    Measured: At 3, 6, 9, 12, 15, 18, 21 and 24 months post HCT

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Dec 2018
  2. Study start29 Aug 2019
  3. Primary completion31 Aug 2027 (estimated)
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03779854
Sponsor's protocol ID
RG1003345
Other IDs
9880, NCI-2018-01752, P30CA015704, RG1003345, P01CA018029-43
Status last verified
Sep 2026
First submitted
17 Dec 2018
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bleakley M. Naive T-cell depletion in stem cell transplantation. Blood Adv. 2020 Oct 13;4(19):4980. doi: 10.1182/bloodadvances.2020001888.

    PubMed 33049057

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Total-Body Irradiation, Thiotepa and Fludarabine in people with Acute Biphenotypic Leukemia and Acute Leukemia, run by Fred Hutchinson Cancer Center at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility achievement (time frame: Up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03779854, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.

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