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

Primary Purpose

Ewing Sarcoma, Gastrointestinal Tumor, Germ Cell Tumor

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
alemtuzumab
fludarabine
sirolimus
Busulfan
melphalan
stem cells
CliniMACS
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ewing Sarcoma

Eligibility Criteria

2 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Feasibility of haploidentical HSCT
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
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
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)
Defined based on any death. The Kaplan-Meier Estimate will be provided.
event-free survival
The Kaplan-Meier Estimate will be provided.

Full Information

First Posted
June 19, 2012
Last Updated
October 14, 2020
Sponsor
St. Jude Children's Research Hospital
Collaborators
CURE Childhood Cancer, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01625351
Brief Title
A Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas
Official Title
A Phase I Study of CD45RA+ Depleted Haploidentical Stem Cell Transplantation in Children With Relapsed or Refractory Solid Tumors and Lymphomas
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
August 20, 2012 (Actual)
Primary Completion Date
February 10, 2020 (Actual)
Study Completion Date
February 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
CURE Childhood Cancer, Inc.

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
alemtuzumab
Other Intervention Name(s)
CAMPATH-1H, Campath(R)
Intervention Description
Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).
Intervention Type
Drug
Intervention Name(s)
fludarabine
Other Intervention Name(s)
Fludara(R)
Intervention Description
Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)
Intervention Type
Drug
Intervention Name(s)
sirolimus
Other Intervention Name(s)
Rapamycin, Rapamune(R)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex(R), Myleran(R)
Intervention Description
Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)
Intervention Type
Drug
Intervention Name(s)
melphalan
Other Intervention Name(s)
L-phenylalanine mustard, phenylalanine mustard, L-PAM, L-sarcolysin
Intervention Description
Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)
Intervention Type
Biological
Intervention Name(s)
stem cells
Other Intervention Name(s)
HSCT, Stem cell transplantation
Intervention Description
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.)
Intervention Type
Device
Intervention Name(s)
CliniMACS
Other Intervention Name(s)
Cell Selection System
Intervention Description
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.
Primary Outcome Measure Information:
Title
Feasibility of haploidentical HSCT
Description
Feasibility is defined as engraftment (ANC≥ 500/mm3 for 3 consecutive tests performed on different days) evaluated before day +30.
Time Frame
30 days post transplantation
Secondary Outcome Measure Information:
Title
hematopoietic cell recovery and engraftment rates
Description
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.
Time Frame
30 days post transplantation
Title
infection rates and complications
Description
The proportion of patients who develop infections and complications will be estimated and a Blyth-Still-Casella 95% confidence interval will be provided.
Time Frame
up to 5 years
Title
overall survival (OS)
Description
Defined based on any death. The Kaplan-Meier Estimate will be provided.
Time Frame
up to 1 year after transplantation
Title
event-free survival
Description
The Kaplan-Meier Estimate will be provided.
Time Frame
up to 1 year after transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brando Triplett, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude

Learn more about this trial

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

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