Trial record 14 of 39 for:    Open Studies | "Wilms Tumor"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborator:
CURE Childhood Cancer
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01625351
First received: June 19, 2012
Last updated: August 8, 2014
Last verified: August 2014
  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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]
    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: up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 5 years ] [ Designated as safety issue: No ]
    Defined based on any death. The Kaplan-Meier Estimate will be provided.

  • event-free survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    The Kaplan-Meier Estimate will be provided.


Estimated Enrollment: 24
Study Start Date: July 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (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.

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

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
Genders Eligible for Study:   Both
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

Contacts
Contact: David R. Shook, MD 866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: David R. Shook, MD    866-278-5833    info@stjude.org   
Principal Investigator: David R. Shook, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
CURE Childhood Cancer
Investigators
Principal Investigator: David R. Shook, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01625351     History of Changes
Other Study ID Numbers: RADIANT
Study First Received: June 19, 2012
Last Updated: August 8, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014