Stem Cell Transplant for Leukemia

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

14 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment CliniMACS CD34+ Reagent System for leukemia?

Research shows that using the CliniMACS system to select CD34+ cells for transplantation is effective and well-tolerated in high-risk leukemia patients, with 62.5% of patients alive and in remission after treatment. Additionally, in a study involving Mexican children with leukemia, successful engraftment was achieved in three out of four cases, although infection risks were noted. ^{1 2 3 4 5}

Is the CliniMACS CD34+ Reagent System safe for use in humans?

The CliniMACS CD34+ Reagent System has been used in various studies for stem cell transplants, showing it to be generally safe. No severe complications were observed in the first 100 days in one study, and another study confirmed the safety of the procedure in adult patients with autologous transplants. However, there is a risk of infections, as seen in some patients. ^{1 4 6 7 8}

How is the CliniMACS CD34+ Reagent System treatment different from other leukemia treatments?

The CliniMACS CD34+ Reagent System is unique because it involves selecting specific stem cells (CD34+ cells) from a donor to reduce the risk of complications like graft-versus-host disease (a condition where the donor's immune cells attack the recipient's body) and improve engraftment success. This approach is particularly beneficial for high-risk patients and those with mismatched donors, offering a more targeted and potentially safer alternative to traditional bone marrow transplants. ^{1 2 4 5 9}

What is the purpose of this trial?

The purpose of this study is to learn more about the effects of (classification determinant) CD34+ stem cell selection on graft versus host disease (GVHD) in children, adolescents, and young adults. CD34+ stem cells are the cells that make all the types of blood cells in the body. GVHD is a condition that results from a reaction of transplanted donor T-lymphocytes (a kind of white blood cell) against the recipient's body and organs. Study subjects will be offered treatment involving the use of the CliniMACS® Reagent System (Miltenyi Biotec), a CD34+ selection device to remove T-cells from a peripheral blood stem cell transplant in order to decrease the risk of acute and chronic GVHD. This study involves subjects who are diagnosed with a malignant disease, that has either failed standard therapy or is unlikely to be cured with standard non-transplant therapy, who will receive a peripheral blood stem cell transplant. A malignant disease includes the following: Chronic Myeloid Leukemia (CML) in chronic phase, accelerated phase or blast crisis; Acute Myelogenous Leukemia (AML); Myelodysplastic Syndrome (MDS); Juvenile Myelomonocytic Leukemia (JMML); Acute Lymphoblastic Leukemia (ALL); or Lymphoma (Hodgkin's and Non-Hodgkin's).

Research Team

Diane George, MD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Haploidentical bone marrow transplantation in Mexico. [2012]

2. China pubmed.ncbi.nlm.nih.gov

[Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia]. [2018]

3. Malaysia pubmed.ncbi.nlm.nih.gov

Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience. [2008]

4. United States pubmed.ncbi.nlm.nih.gov

Allogeneic transplantation of selected peripheral CD34+ cells with controlled CD3+ cells add-back in high-risk patients. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A CD34+ Cell Enrichment Protocol of Hematopoietic Stem Cells in a Well-Established Quality Management System. [2020]

7. Slovakia 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. [2006]

8. United States pubmed.ncbi.nlm.nih.gov

CD34+ cell enrichment for autologous peripheral blood stem cell transplantation by use of the CliniMACs device. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Tolerance induction by "megadose" hematopoietic transplants: donor-type human CD34 stem cells induce potent specific reduction of host anti-donor cytotoxic T lymphocyte precursors in mixed lymphocyte culture. [2019]