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

NCT01625351 | Completed Phase 1 FDA Drug FDA Device

• 2 other identifiers: RADIANTNCI-2012-00588
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ewing Sarcoma; Gastrointestinal Tumor; Germ Cell Tumor; Hepatic Tumor; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Clear Cell Carcinoma; Renal Cell Carcinoma; Melanoma; Neuroblastoma; Rhabdomyosarcoma; Non-rhabdomyosarcoma

Outcome Measures

Primary Outcomes (1)

• Feasibility of haploidentical HSCT

  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 Outcomes (4)

• hematopoietic cell recovery and engraftment rates

  30 days post transplantation

• infection rates and complications

  up to 5 years

• overall survival (OS)

  up to 1 year after transplantation

• event-free survival

  up to 1 year after transplantation

Study Arms (1)

Treatment

EXPERIMENTAL

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.

Drug: alemtuzumab; Drug: fludarabine; Drug: sirolimus; Drug: Busulfan; Drug: melphalan; Biological: stem cells; Device: CliniMACS

Interventions

alemtuzumab DRUG

Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).

Also known as: CAMPATH-1H, Campath(R)

Treatment

fludarabine DRUG

Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)

Also known as: Fludara(R)

Treatment

sirolimus DRUG

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.

Also known as: Rapamycin, Rapamune(R)

Treatment

Busulfan DRUG

Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)

Also known as: Busulfex(R), Myleran(R)

Treatment

melphalan DRUG

Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)

Also known as: L-phenylalanine mustard, phenylalanine mustard, L-PAM, L-sarcolysin

Treatment

stem cells BIOLOGICAL

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.)

Also known as: HSCT, Stem cell transplantation

Treatment

CliniMACS DEVICE

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.

Also known as: Cell Selection System

Treatment

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• At least 18 years of age.
• Partially HLA matched family member.
• Human immunodeficiency virus (HIV) negative.
• (Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
• (Female only) Breast feeding.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• CURE Childhood Cancer, Inc.: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Sarcoma, Ewing; Digestive System Neoplasms; Neoplasms, Germ Cell and Embryonal; Carcinoma, Hepatocellular; Lymphoma; Wilms Tumor; Rhabdoid Tumor; Adenocarcinoma, Clear Cell; Carcinoma, Renal Cell; Melanoma; Neuroblastoma; Rhabdomyosarcoma

Interventions

Alemtuzumab; fludarabine; Sirolimus; Busulfan; Melphalan; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Liver Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Myosarcoma; Neoplasms, Muscle Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Organic Chemicals; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Brando Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: August 20, 2012
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

US (1)