RADIANT: Donor Hematopoietic Stem Cell Transplant in Treating Young Patients with Relapsed or Refractory Solid Tumors or Lymphomas

A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation In Children with Relasped or Refractory Solid Tumors

Categories:

Bone Marrow Transplant

Solid Tumor

Phase I/II

Diseases Treated:

Relapsed or refractory solid tumors or lymphomas

Eligibility Overview:

  • Between the ages of 2 and 21 years
  • Solid tumor or lymphoma as primary cancer
  • Cancer that has come back or did not respond to previous chemotherapy
  • No heart, kidney or liver problems
  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.

    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.

    Trial Outline

    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.

    Interventions

    • Drugs: Alemtuzumab, fludarabine, sirolimus, busulfan, melphalan
    • Biological: Stem cells

    Study Arm

    Experimental: Treatment

    Participants to undergo transplantation. Participants treated after 06/05/2014 have not and will not receive sirolimus as part of their therapy.

    Eligibility

    Inclusion Criteria for Transplant Recipients:

    • ≥2 years old and ≤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 2 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 principal investigator (PI)
    • Shortening fraction ≥25%
    • Creatinine clearance ≥50 mL/min/1.73 m2
    • Pulse oximetry ≥92% on room air
    • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 times the upper limit of the institution-established normal range
    • Direct bilirubin ≤3.0 mg/dL
    • Karnofsky or Lansky performance score of ≥50

    Exclusion Criteria for 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)
    • Pregnancy (negative serum or urine pregnancy test to be conducted within 7 days before enrollment)
    • Breastfeeding

    Inclusion Criteria for Donors:

    • ≥18 years old
    • Partially HLA-matched family member
    • Human immunodeficiency virus (HIV) negative

    Exclusion Criteria for Donors:

    • Pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment)
    • Breastfeeding
  2. About this clinical trial

    St. Jude has pioneered a process known as a haploidentical transplant, which uses a donor—usually a parent—who is a partial “match” to the patient’s immune type.

    In this Phase I clinical trial, St. Jude researchers want to find out how well a new kind of therapy using haploidentical stem cell transplantation works in treating participants with solid tumors and lymphomas that have come back or did not respond to previous treatment.

    Stem cell transplantation is a kind of treatment that uses the immune system to try to fight the cancer, rather than attacking the cells directly with chemotherapy or radiation. Stem cells will be provided to participants by a related donor.

    Treatment

    Treatment will be done in 2 steps

    • Chemotherapy to reduce or destroy the bone marrow within your child’s bones, and any remaining cancer cells. This is done to make room for the new, healthy bone marrow cells that will come from a family member donor.
    • Stem cell transplantation using healthy stem cells from the bone marrow of a family member to help restore and rebuild your child’s bone marrow and his or her immune- and blood-cell-forming systems.

    Follow up – After the stem cell transplant is completed, patients will be evaluated at least once a year for 10 years.

    Eligibility overview

    • Between the ages of 2 and 21 years
    • Solid tumor or lymphoma as primary cancer
    • Cancer that has returned or did not respond to previous chemotherapy
    • No heart, kidney or liver problems

Contact

Brandon Triplett, MD

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

Referring or consulting clinicians only: protocolinfo@stjude.org
For all other inquiries about St. Jude Children's Research Hospital studies: referralinfo@stjude.org

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