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

NCT ID: NCT01625351

Last Updated: 2020-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-20
• Study Completion Date: 2020-02-10

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

alemtuzumab

Intervention Type: DRUG

Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).

fludarabine

Intervention Type: DRUG

Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)

sirolimus

Intervention Type: DRUG

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.

Busulfan

Intervention Type: DRUG

Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)

melphalan

Intervention Type: DRUG

Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)

stem cells

Intervention Type: BIOLOGICAL

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.)

CliniMACS

Intervention Type: DEVICE

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.

Interventions

alemtuzumab

Patients receive alemtuzumab on days -14 through -12 (Day 0 = stem cell transplantation).

Intervention Type: DRUG

fludarabine

Patients receive fludarabine phosphate on days -11 through -7. (Day 0 = stem cell transplantation.)

Intervention Type: 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.

Intervention Type: DRUG

Busulfan

Patients receive busulfan on days -6 through -3. (Day 0 = stem cell transplantation.)

Intervention Type: DRUG

melphalan

Patients receive melphalan on days -2 and -1. (Day 0 = stem cell transplantation.)

Intervention Type: DRUG

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.)

Intervention Type: BIOLOGICAL

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.

Intervention Type: DEVICE

Other Intervention Names

CAMPATH-1H; Campath(R); Fludara(R); Rapamycin; Rapamune(R); Busulfex(R); Myleran(R); L-phenylalanine mustard; phenylalanine mustard; L-PAM; L-sarcolysin; HSCT; Stem cell transplantation; Cell Selection System

Eligibility Criteria

Inclusion Criteria

• 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.

• At least 18 years of age.
• Partially HLA matched family member.
• Human immunodeficiency virus (HIV) negative.

Exclusion Criteria

• 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.

• (Female only) Known pregnancy (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
• (Female only) Breast feeding.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CURE Childhood Cancer, Inc.

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brando Triplett, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2012-00588

Identifier Type: REGISTRY

Identifier Source: secondary_id

RADIANT

Identifier Type: -

Identifier Source: org_study_id