A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

February 4, 2026 updated by: St. Jude Children's Research Hospital

A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

This is a phase I study designed to determine the feasibility of transplantation using a novel transplant approach that employs a two-stage haploidentical cell infusion following myeloablative conditioning. This strategy, which includes selective depletion of naïve T cells, may speed immune reconstitution thereby potentially reducing the limitations of traditional haploidentical hematopoietic stem cell transplantation (HSCT) and increasing its potential therapeutic application. Additionally, the investigators intend to explore overall survival, event-free survival, hematopoietic cell recovery and engraftment as well as infection rates and complications in these patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Twelve participants and 12 donors will be enrolled on this study. Donors will undergo seven days of hematopoietic stem cell (HSC) mobilization followed by two apheresis collections. Each apheresis collection will be processed by the CliniMACS system.

DONORS: A mobilization regimen of granulocyte colony stimulating factor (G-CSF) will be used to obtain a peripheral blood stem cell (PBSC) product from the donor. Apheresis will be performed for a minimum of two consecutive days, including one day for each cell product delivered.

STUDY PARTICIPANTS: Participants will undergo a two-stage haploidentical cell infusion following myeloablative conditioning. The first cell infusion will be a CD3-depleted product and the second infusion will be a CD45RA-depleted product.

Primary Objective:

  • To determine the feasibility of haploidentical HSCT using two infusions engineered by negative selection on the Miltenyi CliniMACS system- the first by selective depletion of CD3+ cells, followed by a second depleted of CD45RA+ cells, in children with relapsed or refractory solid tumors or lymphomas.

Secondary Objectives:

  • To estimate hematopoietic cell recovery and engraftment rates for the patients.
  • To estimate infection rates and complications.
  • To estimate the one-year overall survival (OS) and event-free survival (EFS) for the study patients.

Study Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

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.

Eligibility Criteria

Ages Eligible for Study

2 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria - Transplant Recipients:

  • At least 2 years of age and less than or equal to 21 years of age.

  • Histologically confirmed solid tumor or lymphoma at original diagnosis:

    • Ewing Sarcoma Family of Tumors (ESFT)
    • Gastrointestinal tumors
    • Germ Cell tumors
    • Hepatic tumors (including hepatocellular carcinoma and hepatoblastoma)
    • Lymphoma (including Hodgkin and non-Hodgkin lymphoma)
    • Kidney tumors (including Wilms tumor, rhabdoid tumors, clear cell carcinoma, and renal cell carcinoma)
    • Melanoma
    • Neuroblastoma
    • Soft tissue sarcoma (including rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcoma)
  • Malignancy has no reasonable expectation of cure with available alternative salvage therapy.
  • Has a suitable human leukocyte antigen (HLA) haploidentical donor available.
  • At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation therapy.
  • Has recovered from all acute NCI Common Toxicity Criteria grade II-IV acute non-hematologic toxicities from prior therapy per the judgment of the PI.
  • Shortening fraction greater than or equal to 25%.
  • Creatinine clearance or glomerular filtration rate (GFR) greater than or equal to 50 mL/min/1.73 m2.
  • Pulse oximetry greater than or equal to 92% on room air
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) less than or equal to3 times the upper limit of the institution-established normal range.
  • Direct bilirubin less than or equal to 3.0 mg/dL.
  • Karnofsky or Lansky performance score of greater than or equal to 50.

Exclusion Criteria - Transplant Recipients:

  • Newly diagnosed patients with no prior attempt at curative therapy.
  • Any primary or active central nervous system (CNS) malignancy, including metastatic disease.
  • Any active or prior malignant or pre-malignant condition of the bone marrow, excluding metastasis of the primary malignancy.
  • Prior allogeneic hematopoietic stem cell transplant.
  • Prior autologous stem cell transplant within previous 3 months.
  • Allergy to murine products or positive human anti-mouse antibody (HAMA).
  • (Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
  • (Female only) Breast feeding.

Inclusion Criteria - Donors:

  • At least 18 years of age.
  • Partially HLA matched family member.
  • Human immunodeficiency virus (HIV) negative.

Exclusion Criteria - Donors:

  • (Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
  • (Female only) Breast feeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment

Participants to undergo transplantation. They receive alemtuzumab, fludarabine, sirolimus, busulfan, melphalan, and stem cells.

Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.

Cells for infusion are prepared using the CliniMACS System.
Device: CliniMACS
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Other Names:
  • Cell Selection System
Drug: alemtuzumab
Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).
Other Names:
  • CAMPATH-1H
  • Campath(R)
Drug: fludarabine
Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)
Other Names:
  • Fludara(R)
Drug: sirolimus

Patients receive sirolimus beginning on day -1 with taper beginning on day 90. (Day 0 = stem cell transplantation.)

Participants treated after activation of protocol revision 2.3 on 06/05/2014 have not and will not receive sirolimus as part of their therapy.

Other Names:
  • Rapamycin
  • Rapamune(R)
Drug: Busulfan
Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)
Other Names:
  • Busulfex(R)
  • Myleran(R)
Drug: melphalan
Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)
Other Names:
  • L-PAM
  • L-phenylalanine mustard
  • L-sarcolysin
  • phenylalanine mustard
Biological: stem cells
Patients undergo CD3 depleted haploidentical hematopoietic stem cell transplant (HSCT) on day 0. Patients also undergo CD45RA depleted HSCT infusion on day 1. (Day 0 = stem cell transplantation.)
Other Names:
  • HSCT
  • Stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of haploidentical HSCT
Time Frame: 30 days post transplantation
Feasibility is defined as engraftment (ANC≥ 500/mm3 for 3 consecutive tests performed on different days) evaluated before day +30.
30 days post transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
hematopoietic cell recovery and engraftment rates
Time Frame: 30 days post transplantation
They will be reported and presented descriptively. Specifically, the hematopoietic cell recovery and engraftment rates will be reported with a Blyth-Still-Casella 95% confidence interval.
30 days post transplantation
infection rates and complications
Time Frame: up to 5 years
The proportion of patients who develop infections and complications will be estimated and a Blyth-Still-Casella 95% confidence interval will be provided.
up to 5 years
overall survival (OS)
Time Frame: up to 1 year after transplantation
Defined based on any death. The Kaplan-Meier Estimate will be provided.
up to 1 year after transplantation
event-free survival
Time Frame: up to 1 year after transplantation
The Kaplan-Meier Estimate will be provided.
up to 1 year after transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Collaborators

CURE Childhood Cancer, Inc.

Investigators

  • Principal Investigator: Brando Triplett, MD, St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

August 20, 2012

Primary Completion (Actual)

February 10, 2020

Study Completion (Actual)

February 10, 2020

Study Registration Dates

First Submitted

June 19, 2012

First Submitted That Met QC Criteria

June 20, 2012

First Posted (Estimated)

June 21, 2012

Study Record Updates

Last Update Posted (Actual)

February 6, 2026

Last Update Submitted That Met QC Criteria

February 4, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RADIANT
  • NCI-2012-00588 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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