Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Carboplatin

Etoposide

Melphalan

Etoposide phosphate

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Stem Cell Transplantation of CD133+ cells using the ClinicMACS in combination with Carboplatin + Etoposide + Melphalan

Carboplatin by vein over 24 hours for 4 days, dosing as determined at day 1.

300 mg/m\^2 by vein over 24 hours for 4 days

Stem Cell Infusion (approximately 5x10\^8 TNC cells/kg CD133+ selected) on Day 0.

Stem Cell Infusion

Device used to process the blood and separate the CD 133+ cells needed for transplantation

ClinicMACS

Laura L. Worth, MD, PhD

The goal of this clinical research study is to learn how long it takes for certain types of transplanted stem cells to produce new blood cells. The safety of this treatment will also be studied. Finally, researchers want to learn if collecting the cells with the CliniMACS device can decrease the possibility of tumor cells contaminating (appearing in) the stem cells that are reinfused into participants.

Researchers want to learn if a CD133+ selected autologous stem cell transplant can help to control the disease in patients with high-risk neuroblastoma. After your cells are collected, they will be treated in the cell processing lab using the CliniMACS device. This device will separate out the CD133+ cells. These selected cells will then be given back to you on the day of transplant.

If you are found to be eligible to take part in this study, you will have a small plastic tube placed in the collar bone area or the femoral vein (groin area). This is called a central venous catheter (CVC). You will sign a separate consent form for the CVC placement and the general anesthesia that is given. There may be several weeks between the collection of stem cells and the reinfusion of these cells after high-dose chemotherapy. If the CVC is placed in the femoral vein, the CVC will be removed after the stem cells are collected and a new CVC will be placed in the collar bone before you are admitted for the stem cell transplant. The CVC will be used for chemotherapy, fluids, blood products, stem cells, and other medications. The CVC will remain until it is no longer needed (usually 2-3 months).

To help move the needed stem cells from your bone marrow to your blood, a drug called granulocyte colony-stimulating factor G-CSF (filgrastim) will be injected under the skin. These injections may be given once a day for Days 2-7. You or your caregiver will be taught how to give the injections at home. After 2 days of filgrastim injections, a blood sample (about 4 teaspoons each time) will be drawn each day until you begin leukapheresis. This blood test is used to check the number of stem cells and to watch for possible side effects. You will then be instructed to either continue with the daily injections or stop. When the number of stem cells in the blood is high enough, you will go to the MD Anderson Apheresis Unit to have your stem cells collected.

The procedure to collect your stem cells is called leukapheresis. It is similar to donating platelets to a blood bank. For this procedure, the stem cells will be removed from the blood through the CVC, and the remaining blood will be given back to you through the CVC. You will have one leukapheresis procedure per day, for 1-5 days in a row, until enough stem cells are collected for the transplant. "Back-up" cells (extra cells collected during the leukapheresis procedure) will also be collected. These cells will be stored in the cell processing lab and may given back to you later if your white cell count does not recover. Each leukapheresis procedure takes about 4-6 hours. This research study will use the CliniMACS device to process the blood and separate the cells needed for transplantation. Researchers will test a small sample of the collected cells to see if any tumor cells that might be present in the blood before using the CliniMACS device are no longer present in the processed blood after using the device.

Carboplatin and etoposide are designed to interfere with the growth of cancer cells by stopping cell division, and melphalan is designed to damage the DNA (the genetic material) of cells. The combination of carboplatin, etoposide, and melphalan causes a large amount of bone marrow cells to die, which stops blood cells from being produced as normal. In order to try to restart the production of blood cells, an autologous stem cell transplant is often performed. For an autologous transplant, stem cells are removed from the blood. Usually when stem cells are collected, they are either given back to the patient as collected, or else a smaller group of cells that have a certain "marker" on their cell surface is selected (separated out) before being given back to the patient. The CliniMACS device is a machine that processes blood and separates the cells needed for transplantation. The CliniMACS device is designed to select stem cells with a different marker on the cell surface than is normally selected. The marker is called CD133+, and researchers believe that transplanting cells that have this marker will make the infused cells less likely to be contaminated with neuroblastoma cells, compared to the standard method of cell selection.

After 5 days of leukapheresis procedures, if the number of stem cells collected is lower than a certain level, you will no longer be eligible to take part in the study.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. If these tests have been performed recently, they may not need to be repeated. To check the status of the disease, you will have CT scans, bone marrow aspirations and biopsies, and a chest x-ray. The CT scans will be performed on the chest, abdomen, and pelvis (and if needed, the brain). To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. You will have a pulmonary function test (to measure lung function), an echocardiogram (to measure heart function), and an electrocardiogram (EKG -- a test to measure the electrical activity of the heart). You will have a physical exam, including measurement of vital signs (such as blood pressure and heart rate), height, and weight. Blood (about 4 tablespoons) will be drawn for routine tests and to check for diseases such as hepatitis and HIV. Females who are able to have children must have a negative urine pregnancy test. You will also have a 12 or 24-hour urine test before carboplatin can be given. For this test, you will collect your urine over 12 or 24 hours. You will be provided with a container to collect the urine in. This test will be used to help decide the dosing of carboplatin that you receive.

After enough stem cells are collected, and at a time decided upon by your neuro-oncologist and transplantation doctors, you will be admitted to the hospital to receive fluids and then the chemotherapy drugs carboplatin, etoposide, and melphalan, according to the standard schedule. After the chemotherapy, you will have 3 "rest" days where no chemotherapy is given.

On the day after the third rest day, your stem cells will be infused back into your CVC. To help speed up the recovery of your white blood cells, a drug called filgrastim will be injected under the skin. You will receive a filgrastim injection under the skin once a day, until the white blood cell count recovers (usually 2-3 weeks). You may also receive standard antibiotics, fluids, and/or other medications, if your doctor feels it is necessary based on symptoms you may have. While you are in the hospital, you will have physical exams once a day. Blood (about 4 teaspoons each time) will be drawn about 3-7 days per week, until your blood counts are fully recovered and any side effects of the chemotherapy have resolved. At that time, you will be able to leave the hospital.

From the time you leave the hospital until about Day 60, you will have follow-up visits at least once per week. At these visits, you will have a physical exam. Blood (about 4 teaspoons each time) will be drawn for routine tests. However, your participation in this study will not be over until after your annual follow-up at which time you will have a medical history and physical exam, blood (about 4 teaspoons) drawn for routine tests, and a CT scan.

If the disease gets worse or intolerable side effects occur at any time in this study, you will be taken off study.

This is an investigational study. All of the drugs used in this study are commercially available and FDA approved for use in neuroblastoma. The CliniMACS device is not commercially available or FDA approved. It has been authorized for use in research only.

Up to 20 patients will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson.

Autologous Stem Cell Rescue With CD133+ Selected Cells in High-Risk Neuroblastoma

Autologous Stem Cell Rescue With CD133+ Selected Hematopoietic Progenitor Cells in Patients With High-Risk Neuroblastoma

Engraftment failure is defined as if by day +42 participant does not have an absolute neutrophil count (ANC) \>500/ul, and has no evidence of donor chimerism on bone marrow examination.

Engraftment Failure Rate is number of participants with engraftment failure out of total participants. Engraftment failure is defined as failure to achieve an absolute neutrophil count (ANC) \>500/ul by day 42, and has no evidence of donor chimerism on bone marrow examination.

Toxicity associated with CliniMACS device associated with transplantation of CD133+ cells in high-risk neuroblastoma. Adverse events assessed and graded according to NCI's Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

M.D. Anderson Cancer Center

Stem Cell Transplantation of CD133+ cells using the ClinicMACS in combination with Carboplatin + Etoposide + Melphalan

Carboplatin: Carboplatin by vein over 24 hours for 4 days, dosing as determined at day 1.

Etoposide: 300 mg/m\^2 by vein over 24 hours for 4 days

Melphalan: 70 mg/m\^2 Intravenous Bolus for 3 Days

Stem Cell Infusion: Stem Cell Infusion (approximately 5x10\^8 TNC cells/kg CD133+ selected) on Day 0.

ClinicMACS: Device used to process the blood and separate the CD 133+ cells needed for transplantation

Transplantation CD133+ Cells

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

A final summary or analysis was not possible as only 3 out of 20 planned participants were registered.

Early termination leading to small numbers of subjects analyzed, rare patient population.

Laura L. Worth, MD / Professor, Pediatrics

Study analysis not possible due to small number of participants. Of the 3 participants enrolled, 0 had engraftment failure.

Engraftment Failure Rate

Number of Participants With Device-related Toxicity Associated With Transplantation of CD133+ Cells

Three subjects engrafted after receiving the investigational product, no other analysis available. Of the 3 participants enrolled, 0 had engraftment failure.

Number of Treated Participants With Engraftment Failure at Day 42

Overall Study

Blood and Lymph Conditions

Immune System Diseases

Hematologic Neoplasms

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

* The stem cell apheresis product will be depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.
* CD34+ stem cell counts will be obtained before and after processing with the Miltenyi ClinicMACs device

The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to participants

ClinicMACs

Vincent T Ho, MD

This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.

The device used to remove the α/βT cells in this study is:

-CliniMACS® TCR α/β Reagent System

Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).

The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.

GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:

* Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
* Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.

To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.

In this research study, the investigator are investigating a pre-transplant intervention aimed to prevent GVHD by processing the donor product with the Miltenyi CliniMACS TCR α/β Reagent System. The Reagent System will remove certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it is given to the participant. By selectively removing this specific type of T cells from the donor product, the investigators hope to reduce the risk for GVHD without reducing the efficacy of the transplant.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved CliniMACS α/β T cell depletion system for use in the US, but this system is approved by the European Medicines Agency (EMA) and used in Europe

Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies

Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT

Grades II-IV acute GVHD will be assessed at 2 years post-SCT. Grade I GVHD is characterized as mild disease, grade II as moderate, grade III as severe, and grade IV as life-threatening. Higher grades of acute GVHD are associated with worse outcomes. Acute GVHD will be staged by assessment of clinical manifestations in the skin, gastrointestinal tract, and liver.

Number of participants with chronic GVHD will be assessed at 2 years post-SCT.

GRFS will be defined as alive without having experienced grade III-IV acute GVHD, moderate/severe chronic GVHD, or relapse of underlying malignancy.

Number of participants with immunosuppression-free survival will be assessed at 2 years post-SCT.

Hematologic recovery will be assessed in participants at 2 years post-SCT.

Immune reconstitution will be assessed in participants at 2 years post-SCT.

Disease relapse will be assessed in participants at 2 years post-SCT.

Participant transplant-related mortality will be assessed at 2 years post-SCT.

Participant organ toxicity will be assessed at 2 years post-SCT.

Participant rate of infections will be assessed at 2 years post-SCT.

Number of participants with relapse-free and overall survival will be assessed at 2 years post-SCT.

Dana-Farber Cancer Institute

Principal Investigator

Adverse events were collected through regular investigator assessment and laboratory testing.

The stem cell apheresis product was depleted of TCRαβ T cells by negative selection using the automated CliniMACS® Plus device.

CD34+ stem cell counts were obtained before and after processing with the Miltenyi ClinicMACs device.

ClinicMACs: The Reagent System removed certain cells (called T-Cell Receptor (TCR) α/β positive T-cells) that are thought to cause GVHD from donor product before it was given to participants.

TCR α/β Reagent System

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Only evaluable participants, defined as participants who received investigational product, are included in the analysis population. Therefore, participants who never started protocol treatment have been excluded.

Early termination after accrual of only one evaluable subject resulted in an insufficient sample size for analysis.

Dr. Vincent Ho

Number of Participants With Severe Acute GVHD-free Survival

No participants were analyzed for this secondary outcome measure, because the only participant who would have been evaluable for analysis did not survive to the analysis timepoint of 2 years post-transplant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous Stem Cell Rescue With CD133+ Selected Cells in High-Risk Neuroblastoma	NCT00539500	Neuroblastoma	Carboplatin Etoposide Melphalan Stem Cell Infus... ClinicMACS	-	M.D. Anderson Cancer Center
Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies	NCT03717480	Hematologic Mal...	ClinicMACs	18 Years - 65 Years	Dana-Farber Cancer Institute
Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies	NCT03717480	Hematologic Mal...	ClinicMACs	18 Years - 65 Years	Dana-Farber Cancer Institute
Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies	NCT03717480	Hematologic Mal...	ClinicMACs	18 Years - 65 Years	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for clinicmacs

Every month we try and update this database with for clinicmacs cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for clinicmacs

Every month we try and update this database with for clinicmacs cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for clinicmacs cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.