Clinical trial NCT01625351: 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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: CURE Childhood Cancer, Inc.
First posted: 2012-06-21
Enrollment: 23
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Feasibility of haploidentical HSCT
timeFrame: 30 days post transplantation
Secondary outcomes:
measure: hematopoietic cell recovery and engraftment rates
timeFrame: 30 days post transplantation
measure: infection rates and complications
timeFrame: up to 5 years
measure: overall survival (OS)
timeFrame: up to 1 year after transplantation
measure: event-free survival
timeFrame: up to 1 year after transplantation
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Brando Triplett, MD
role: PRINCIPAL_INVESTIGATOR
References: