Stem Cell Transplant for Lymphoma

Overseen By Chowdury Nazma

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Disqualifiers: Non-compliance, No caregivers, Uncontrolled disorders, Allergy to DMSO, Pregnant/breastfeeding, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1-2 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Patients with graft failure or delayed engraftment may benefit from a hematopoietic stem cell boost or an additional hematopoietic stem cell transplantation procedure. In such settings standard immune suppression strategies are avoided due to their myelosuppressive nature. Therefore those patients are at increased risk of graft versus host disease, and the infusion of a CD34 selected graft would reduce such a risk. The infusion of CD34 selected graft using CliniMACS plus is currently FDA FDA-approved indication for acute myeloid leukemia. However, the use of the Prodigy would streamline the processing, in terms of hands-off procedure, allowing to provision of this product to the patients without strains on the cell therapy lab team. This procedure has been demonstrated safe and effective in several single-center studies and is currently in advanced phase investigation in several studies for malignant and non-malignant conditions.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since standard immune suppression strategies are avoided, it's possible that some medications might need to be adjusted. Please consult with the trial team for specific guidance.

What data supports the effectiveness of the treatment Infusion of CD34 selected hematopoietic stem cells for lymphoma?

Research shows that using CD34+ selected stem cells in transplants for lymphoma can lead to successful engraftment (when the new cells start to grow and make healthy blood cells) and has been used in various types of lymphoma treatments. Although the dose of stem cells can affect the speed of recovery, it does not seem to impact overall survival rates. ^{1 2 3 4 5}

Is stem cell transplant for lymphoma safe?

Stem cell transplants can have some risks, including serious reactions like low blood pressure, heart rhythm problems, and breathing issues, but these are rare. Most people experience mild side effects like fever, chills, or nausea, and careful monitoring by medical staff helps manage these risks. ^{1 6 7 8 9}

How does the stem cell transplant treatment for lymphoma differ from other treatments?

This stem cell transplant treatment for lymphoma is unique because it involves using CD34+ cell selection to enrich blood stem cells, which can help patients who have undergone intense chemotherapy and radiotherapy. This approach is different from standard chemotherapy as it aims to restore the patient's blood and immune system using their own or a donor's stem cells, potentially offering better outcomes for those with advanced or recurrent lymphoma. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for patients with certain blood cancers or tumors who have had a stem cell transplant that didn't work well. They should be in remission or have specific disease features, and not allergic to DMSO. Pregnant women, those without caregivers, non-compliant individuals, or anyone with uncontrolled health issues can't join.

Inclusion Criteria

My lymphoid cancer is responding to treatment.

My condition is a type of blood disorder with less than or equal to 10% immature blood cells.

My CML is in remission after a more severe phase.

Exclusion Criteria

Non-compliant patients

Uncontrolled medical or psychiatric disorders which may preclude patients to undergo clinical studies (Discretion of the attending physician)

Pregnant or breastfeeding women

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a CD34 selected hematopoietic stem cell infusion with or without preceding conditioning

1-2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 years

Treatment Details

Interventions

• Infusion of CD34 selected hematopoietic stem cells

Trial Overview The trial tests the infusion of CD34 selected hematopoietic stem cells using CliniMACS Prodigy to reduce graft versus host disease risk after a failed stem cell transplant. It's designed to make the process easier on lab teams and has shown promise in previous studies.

Participant Groups

Group I: Treatment population Experimental Treatment 1 Intervention

Patients status post allogeneic hematopoietic stem cell transplantation for a neoplastic hematologic disorder with the need of a CD34 selected stem cell boost for graft failure or low graft function will receive a CD34 selected hematopoietic stem cell infusion with or without preceding conditioning. Fludarabine 25 mg/mq day 1 - 5 + 2 Gray Total body irradiation depending on clinician's discretion (with the addition of cyclophosphamide 14.5 mg/kg for two doses for haploidentical or matched unrelated donor with at least one major HLA mismatch). Recommendation to use a conditioning regimen include complete loss of donor chimerism, trilineage cytopenias.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

The review of 18 studies on hematopoietic stem cell transplantation found that mild and moderate adverse reactions were most common, with nausea and vomiting being the most frequently reported issues.

The cardiovascular, respiratory, and gastrointestinal systems were the most affected by these adverse reactions, highlighting the need for monitoring these organ systems during and after the infusion of stem cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions on day zero of hematopoietic stem cell transplantation: integrative review. Figueiredo, TWB., Mercês, NNAD., Nunes, MBM., et al.[2022]

In a study of 213 pediatric patients undergoing hematopoietic stem cell transplantation, serious adverse reactions (ARs) during cellular therapy product infusions occurred in 25% and 11% of cases, with no severe grade 4 or 5 reactions reported.

The source of stem cells significantly influenced the risk of serious ARs, with cord blood being associated with a higher risk, while manipulated cellular therapy products were found to be protective, suggesting they can help reduce adverse reactions during infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. Truong, TH., Moorjani, R., Dewey, D., et al.[2018]

The study successfully cultured and expanded CD34-positive cells from mobilized peripheral blood, demonstrating the feasibility of this method for clinical use.

Patients tolerated the infusions of these cells well, and successful engraftment was achieved, indicating a positive safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of selected and expanded peripheral blood CD34+ cells: a preliminary report of feasibility and safety. Zimmerman, TM., Williams, SF., Bender, JG., et al.[2004]

Donor leukocyte infusions (DLI) can effectively induce remission in patients who relapse after bone marrow transplantation (BMT), and using CD34+ cell selection allows for the recovery of functional T cells for immunotherapy.

The study found that the CD34+ cell selection process yielded a high recovery of CD3+ T cells (84% responsive) and a significant T cell depletion (99.8%), making it a promising method for generating T cell products for DLI in patients with acute leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A laboratory comparison of T cell depletion by CD34+ cell immunoaffinity selection and in vitro Campath-1M treatment: clinical implications for bone marrow transplantation and donor leukocyte therapy. Clarke, E., Potter, MN., Oakhill, A., et al.[2019]

References

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

Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell transplants for follicular lymphoma: a pilot study. [2017]

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

Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. [2015]

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

Autologous hematopoietic stem cell transplantation with inadequate stem cell dose in patients with non-Hodgkin lymphoma. [2021]

4. China pubmed.ncbi.nlm.nih.gov

[Salvage Trerapy for Patients with Relapsed and Refractory Lymphoma by Allogeneic Hematopoietic Stem Cell Transplantation]. [2018]

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

Allogeneic transplantation for lymphoma: long-term outcome. [2010]

6. Brazil pubmed.ncbi.nlm.nih.gov

Adverse reactions on day zero of hematopoietic stem cell transplantation: integrative review. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. [2018]

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

Toxicities of mobilized stem cell infusion. [2012]

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

Clinical use of selected and expanded peripheral blood CD34+ cells: a preliminary report of feasibility and safety. [2004]

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

Molecular basis for stem cell transplantation in indolent lymphomas. [2007]

11. India pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation. [2019]

12. England pubmed.ncbi.nlm.nih.gov

A laboratory comparison of T cell depletion by CD34+ cell immunoaffinity selection and in vitro Campath-1M treatment: clinical implications for bone marrow transplantation and donor leukocyte therapy. [2019]