Stem Cell Transplant for Leukemia

Not currently recruiting at 1 trial location

Overseen By Desmarie Sherwood

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Diane George

Disqualifiers: Uncontrolled infection, Pregnancy, Breastfeeding

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a special stem cell selection process might reduce the risk of graft versus host disease (GVHD), a condition where transplanted cells attack the body, in young people with certain blood cancers. The treatment uses the CliniMACS® CD34+ Reagent System, a stem cell selection method, to carefully select donor stem cells, aiming to lower the chances of GVHD after a stem cell transplant. The trial includes different groups testing varied preparation methods before the transplant. It is suitable for individuals under 22 with blood-related cancers like leukemia or lymphoma who have not responded to standard treatments. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering a chance to contribute to groundbreaking advancements in blood cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the CliniMACS CD34+ Reagent System is safe for use in stem cell transplants?

Research has shown that the CliniMACS CD34+ Reagent System, used in stem cell transplants, is generally safe for patients with serious blood disorders. It effectively removes certain cells called T-cells, reducing the risk of graft versus host disease (GVHD), which occurs when the donor's cells attack the patient's body.

Several studies have tested the system, and the results support its safety. Most patients tolerate the treatment well. Although some side effects have been reported, they are usually manageable with proper care. The treatment has also proven successful in various conditions, making it a reliable option for those needing a stem cell transplant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about these treatments for leukemia because they use a specialized technique called the CliniMACS CD34+ Reagent System. This system focuses on selecting a specific type of stem cell, CD34+ cells, which are vital for successful transplantation and reducing complications. The treatments also explore different conditioning regimens, including full intensity with and without total body irradiation (TBI), as well as reduced intensity options. These varied approaches aim to improve outcomes by tailoring the treatment intensity to patient needs, potentially offering better survival rates and reducing risks like graft-versus-host disease (GVHD) compared to traditional transplant methods.

What evidence suggests that the CliniMACS CD34+ Reagent System is effective for reducing GVHD in leukemia patients?

Research has shown that the CliniMACS CD34+ Reagent System, used in all treatment arms of this trial, can lower the risk of graft versus host disease (GVHD), a condition where the donor's cells attack the recipient's body after a stem cell transplant. This system removes certain white blood cells called T-cells, which are responsible for this attack. Studies have found that this method greatly reduces the chances of both short-term and long-term GVHD. Additionally, the CliniMACS system effectively collects CD34+ stem cells, which are crucial for creating new blood cells. This method has shown promising results in patients with various types of leukemia and other blood cancers, especially when standard treatments have not succeeded. ^{2 6 7 8 9}

Who Is on the Research Team?

Diane George, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for children and young adults under 22 with certain blood cancers like leukemia or lymphoma, who need a stem cell transplant but standard treatments haven't worked. They must have a matched donor, good heart, kidney, liver, and lung function. Pregnant or breastfeeding individuals and those with uncontrolled infections cannot participate.

Inclusion Criteria

I am younger than 22 years old.

My liver is working well.

My heart is functioning well.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have any untreated infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-conditioning

Patients undergo a pre-conditioning regimen involving various medications to prepare for the stem cell transplant

8-9 days

Daily visits for medication administration

Stem Cell Transplant

Participants receive a peripheral blood stem cell transplant with CD34+ selection to reduce the risk of GVHD

1 day

Inpatient procedure

Post-transplant Monitoring

Participants are monitored for acute GVHD and other complications, with assessments conducted daily while hospitalized and then weekly

Up to 2 years

Daily visits while hospitalized, then weekly and as clinically indicated

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for chronic GVHD and immune reconstitution

Up to 2 years

Regular follow-up visits as clinically indicated

What Are the Treatments Tested in This Trial?

Interventions

• CliniMACS CD34+ Reagent System

Trial Overview The study tests if removing T-cells from the donor's stem cells using CliniMACS CD34+ Reagent System can reduce graft versus host disease after transplant in patients with malignant diseases such as various types of leukemia and lymphoma.

How Is the Trial Designed?

Group I: Reduced intensity Experimental Treatment 6 Interventions

Patients will begin tacrolimus 8 days pre-transplant, and then will receive alemtuzumab on the 3rd-7th day pre-transplant; busulfan twice daily on the 5th-8th day pre-transplant; and fludarabine on the 2nd-7th day pre-transplant. Methylprednisolone will start on day -7.The stem cell infusion will be performed (with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus or sirolimus. For patients with a history of hepatic toxicity and/or high-risk for veno-occlusive disease or other liver toxicity post stem cell transplant, melphalan at 70 mg/m2 will be substituted for Busulfan, followed by fludarabine on the 2nd-7th day before transplant and alemtuzumab on the 3rd-7th day before transplant.

Group II: Full intensity without TBI Experimental Treatment 6 Interventions

Patients will start their pre-conditioning regimen 9 days before their scheduled transplant. Patients will receive busulfan twice daily on the 5th-8th day before transplant, and Melphalan on the 2nd-4th days before transplant and Alemtuzumab on the 1st-5th day before transplant. Subjects will then undergo with their stem cell infusion (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System) and GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after their transplant, and methylprednisolone will start on day -5.

Group III: Full intensity with TBI Active Control 6 Interventions

Patients will start their pre-conditioning regimen on 8 days before scheduled transplant. Fractionated total body irradiation (TBI) will be administered twice daily on the 6th, 7th, and 8th before transplant. Patients will receive Thiotepa on the 4th and 5th day before transplant, Cyclophosphamide on the 2nd and 3rd day before transplant, and Alemtuzumab on the 1st-5th day(s) before transplant. Then the stem cell infusion will be performed (allogeneic family member or ≥ 8/10 HLA matched adult unrelated donor peripheral blood stem cell transplantation with CD34 Selection using CliniMACS CD34+ Reagent System). GVHD prophylaxis will consist of tacrolimus only. Tacrolimus administration will begin on the day after transplant, and methylprednisolone will start on day -5.

Who Is Running the Clinical Trial?

Diane George

Lead Sponsor

Trials

2

Recruited

50+

Published Research Related to This Trial

Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes was performed on four Mexican children with hematological malignancies, showing successful engraftment in three out of four cases over a follow-up period of 9½ years.

Despite the successful engraftment, all patients experienced cytomegalovirus reactivation, and one child died due to graft rejection and infectious complications, highlighting the significant risk of infections associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical bone marrow transplantation in Mexico. Vázquez-Meraz, JE., Arellano-Galindo, J., Mendoza-García, E., et al.[2012]

The CliniMACS Prodigy system allows for a complete recovery (100%) of CD34+ cells after selection, which is crucial for hematology patients undergoing treatment.

This optimization in cell recovery can significantly enhance the effectiveness of therapies that rely on CD34+ cells, improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. Pello, OM., Lanzarot, D., Colorado, M., et al.[2020]

Allogeneic transplantation of CliniMACS-selected peripheral CD34+ cells in high-risk patients showed promising results, with 62.5% of patients alive and in remission after a median follow-up of 815 days.

The procedure was well tolerated, with no severe complications in the first 100 days, although 37.5% of patients experienced severe acute graft-versus-host disease (aGVHD) after receiving nonselected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. Markiewicz, M., Hołowiecki, J., Wojnar, J., et al.[2021]

The study evaluated two methods for T cell depletion in peripheral blood stem cell grafts, finding that the CliniMACS system provided higher purity (94.87%) and recovery (58%) of CD34+ cells compared to the CellPro system, which had a purity of 85.6% and recovery of 24.8%.

Both methods are deemed suitable for preparing stem cell grafts for mismatched transplants in patients with severe hematological disorders and for autologous transplants in autoimmune diseases, but the CliniMACS system is preferred due to its superior efficiency in T cell removal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two different methods for CD34+ selection and T cell depletion in peripheral blood stem cell grafts--our experiences with CellPro, E rosetting and CliniMACS technique. Poloucková, A., Vodvárková, A., Kobylka, P., et al.[2006]

The CliniMACS system effectively purifies CD34+ peripheral blood stem cells (PBSC) from adult patients, achieving a median purity of 97.7% and a recovery rate of 69.5%, indicating its efficiency in reducing tumor cell contamination for autologous transplants.

The procedure demonstrated safety, as it did not affect the viability of the selected cells, and the subsequent autologous transplant showed a median time to neutrophil recovery of 12 days, supporting its use in patients with various malignant diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device. Després, D., Flohr, T., Uppenkamp, M., et al.[2019]

The CliniMACS device effectively selects CD34+ cells from peripheral blood stem cells, achieving a median purity of 79% and a recovery rate of 66% in a study involving eight adult patients with hematologic malignancies.

This method significantly reduces T cell content from a median of 3.1 billion pre-selection to just 7.9 million post-selection, while maintaining high cell viability (98%), which is crucial for safe and effective autologous stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience. Leong, CF., Habsah, A., Teh, HS., et al.[2008]

The use of the CliniMACS Plus system for CD34+ cell enrichment in allogeneic stem cell transplantation achieved an average product purity of 95.66%, indicating a high-quality process that enhances the potential for using partially matched grafts without increasing the risk of graft-versus-host disease.

All end products tested negative for bacterial contamination and endotoxins, demonstrating the safety and reliability of the manufacturing process, which was validated across six different cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System. Kilic, P., Bay, M., Yildirim, Y., et al.[2020]

HLA mismatched hemopoietic stem cell transplants can be successfully performed, as all seven patients in the study achieved engraftment and complete remission after receiving the transplants.

The conditioning regimen of busulfan and cyclophosphamide, with the addition of antithymocyte globulin, was effective, and G-CSF mobilized peripheral blood stem cells proved to be a viable source for these transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia]. Huang, X., Chen, Y., Han, W., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3762249/

Characteristics of CliniMACS® System CD34-Enriched T ... A number of single and multi-center trials have demonstrated favorable outcomes with the use of ex vivo T cell depletion (TCD) for acute myeloid ...

2. miltenyibiotec.com miltenyibiotec.com/US-en/products/cell-therapy/clinimacs-cd34-reagent-system-fda-approved/health-care-professionals/clinical-data.html

Clinical data | Miltenyi Biotec | USA The CliniMACS® CD34 Reagent System was tested in a phase II single-arm multicenter study with a total of 37 patients in first morphologic complete remission ...

3. fda.gov fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/IFU--CliniMACS%C2%AE-CD34-Reagent-System.pdf

CD34 Reagent System The potential risks of using the CliniMACS® CD34 Reagent. System were evaluated via a Data Analysis Protocol (DAP), which retrospectively compared the Day-100, ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/17/NCT01200017/Prot_000.pdf

A Phase II Study Using the CliniMACS® Device for CD34+ ... CliniMACS® CD34+ Reagent System has the advantages of the best T cell depletion efficiency achievable and a very high efficiency of CD34+ cell recovery so ...

5. miltenyibiotec.com miltenyibiotec.com/US-en/products/cell-therapy/clinimacs-cd34-reagent-system-fda-approved/health-care-professionals/the-fda-approved-system/clinimacs-cd34-reagent-system-technology.html

CliniMACS CD34 Reagent System Technology The CliniMACS CD34 Reagent System is a medical device that enables in vitro enrichment of CD34-positive hematopoietic stem cells for graft-versus-host disease ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/44/NCT03093844/ICF_001.pdf

Safety and efficacy of Miltenyi CliniMACS® CD34 Reagent ... stem cells using the Miltenyi CliniMACS® CD34 Reagent system is a safe and efficacy treatment for your high-risk hematologic disorder. The ...

7. static.miltenyibiotec.com static.miltenyibiotec.com/asset/150655405641/document_e92cbvqs1p4dh07vljo0ipad08?content-disposition=inline

CliniMACS CD34 Reference List Allogeneic CD34-selected stem cell boost as salvage treatment of life-threatening infection and severe cytopenias after CAR-T cell therapy.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8432362/

Allogeneic Stem Cell Transplantation with CD34+ ... In this review, we summarize the main characteristics of allogeneic stem cell transplant with CD34+ cell selection including risks of graft failure, GvHD, ...

9. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/11/NCT02162511/Prot_SAP_000.pdf

AN EXPANDED ACCESS STUDY USING THE CLINIMACS ... CliniMACS® CD34+ Reagent System has the advantages of the best T cell depletion efficiency achievable and a very high efficiency of CD34+ cell recovery so that ...