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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with certain blood cancers whose stem cell transplant is not working well. It aims to provide a special boost of stem cells to help the transplant succeed without causing serious immune problems. The trial seeks patients who have had a transplant for conditions like leukemia or lymphoma and are experiencing issues with their graft (transplanted cells). This could suit those diagnosed with blood cancers, such as non-Hodgkin's lymphoma or acute myeloid leukemia, who are in remission but need extra help for their transplant to work better. The treatment involves an infusion of CD34-selected hematopoietic stem cells. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 prior data suggests that this procedure is safe for patients with lymphoma?

Research has shown that the CD34-selected stem cell infusion is generally safe for patients. Previous studies have found that this treatment improves patient outcomes with manageable side effects. One study found that nearly all patients regained normal blood cell levels after receiving this stem cell treatment, indicating its effectiveness and safety. Additionally, the FDA has already approved this procedure for treating acute myeloid leukemia, which adds confidence in its safety. Overall, evidence suggests that the treatment is well-tolerated and effective in helping patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for lymphoma, which often involves chemotherapy or radiation, the new treatment uses CD34 selected hematopoietic stem cells for infusion. This approach is unique because it directly targets graft failure or low graft function following a stem cell transplant. Researchers are excited because this method could potentially enhance donor cell integration and restore healthy blood cell production without the extensive side effects typically associated with chemotherapy and radiation. Additionally, the potential to tailor conditioning regimens based on individual patient needs offers a personalized treatment avenue that could improve outcomes.

What evidence suggests that the infusion of CD34 selected hematopoietic stem cells is effective for lymphoma?

Research has shown that CD34-selected stem cell infusions may help when a stem cell transplant doesn't work well. One study found that 72% of patients responded completely to this treatment, and 80% showed some improvement. Additionally, 54% of patients survived for at least 42 months on average. In this trial, participants will receive CD34-selected stem cell infusions to potentially increase survival rates for lymphoma patients by at least 15% over three years. These findings suggest that CD34-selected stem cell infusions could aid patients with failing transplants in recovering and improving their health. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

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

No appropriate caregivers identified

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721010770

Outcomes with CD34-Selected Stem Cell Boost for Poor ... Complete and overall hematologic response rates were 72% and 80%, respectively. After a median follow-up of 42 months, the actuarial survival rate was 54%.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4764129/

CD34-selected hematopoietic stem cell transplants ... There were no differences in rates of graft rejection, leukemia relapse, treatment-related mortality, RFS and OS. However at 1 year, 54% and 12% of patients ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02646098?cond=cd34&viewType=Table&rank=4&checkSpell=

CD34+ Selected ASCT for Aggressive Lymphomas Outcome(s): The aim of the study is to show ≥ 15% better 3-year overall survival of lymphoma patients having received CD34+ cell selection during autologous ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725001319

82 Outcome Following CD34-Selected Stem Cell Boost for ... Poor graft function is a life-threatening complication following allogeneic hematopoietic stem cell transplantation (SCT) that occurs in 5-27% of patients and ...

5. ashpublications.org ashpublications.org/bloodadvances/article/8/17/4729/516114/Active-infection-at-the-time-of-CD34-selected-stem

Active infection at the time of CD34+ selected stem cell boost ... Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor overall survival. Blood Adv (2024) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4975432/

CD34-selected allogeneic hematopoietic stem cell ... Multiple previous studies have demonstrated a median PFS of only 7–8 months in patients with high-risk cytogenetics after high-dose therapy and autologous stem- ...

7. astctjournal.org astctjournal.org/article/S2666-6367(23)01295-2/fulltext

Efficacy and Safety of CD34+ Stem Cell Boost for Delayed ... Eighteen (95%) patients successfully recovered hematopoiesis after stem cell boost with median time for neutrophil, platelet, and hemoglobin ...