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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
CURE Childhood Cancer, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01625351
First received: June 19, 2012
Last updated: August 17, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
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 Drug: alemtuzumab Drug: fludarabine Drug: sirolimus Drug: Busulfan Drug: melphalan Biological: stem cells Device: CliniMACS Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • 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.

  • overall survival (OS) [ Time Frame: up to 1 year after transplantation ]
    Defined based on any death. The Kaplan-Meier Estimate will be provided.

  • event-free survival [ Time Frame: up to 1 year after transplantation ]
    The Kaplan-Meier Estimate will be provided.


Enrollment: 23
Actual Study Start Date: August 20, 2012
Estimated Study Completion Date: August 19, 2019
Primary Completion Date: April 14, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 Name: 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-phenylalanine mustard
  • phenylalanine mustard
  • L-PAM
  • L-sarcolysin
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
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 Name: Cell Selection System

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.
  Eligibility

Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625351

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
CURE Childhood Cancer, Inc.
Investigators
Principal Investigator: Brando Triplett, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01625351     History of Changes
Other Study ID Numbers: RADIANT
NCI-2012-00588 ( Registry Identifier: NCI Clinical Trial Registration Program )
Study First Received: June 19, 2012
Last Updated: August 17, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Additional relevant MeSH terms:
Lymphoma
Carcinoma
Neoplasms
Carcinoma, Renal Cell
Neuroblastoma
Neoplasms, Germ Cell and Embryonal
Rhabdomyosarcoma
Sarcoma, Ewing
Wilms Tumor
Rhabdoid Tumor
Adenomyoepithelioma
Adenocarcinoma, Clear Cell
Digestive System Neoplasms
Gastrointestinal Neoplasms
Liver Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive

ClinicalTrials.gov processed this record on September 21, 2017