Stem Cell Transplantation for Leukemia

No longer recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Tacrolimus, Methotrexate, MMF

Disqualifiers: CNS involvement, HIV, uncontrolled infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 80

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to make stem cell transplants safer for leukemia patients by preventing Graft-Versus-Host Disease (GVHD), a common side effect where donor cells attack the patient's healthy tissues. The study examines whether removing certain immune cells, specifically through Selective Depletion of CD45RA+ T Cells, from donor stem cells can reduce GVHD while still combating leukemia. It targets patients with types of leukemia who are already scheduled for a stem cell transplant. Those with a history of leukemia or related conditions planning to undergo a transplant might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

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

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that a new method in stem cell transplants, which involves removing certain T cells, may reduce the risk of acute graft-versus-host disease (GVHD). GVHD occurs when donor cells attack the patient's healthy tissues after a transplant, a common concern. One study found that the chance of developing moderate to severe GVHD within 28 days of the transplant was 0% at one dose level, 20% at another, and 10% at a third.

This method aims to retain the beneficial effects of donor T cells while minimizing their harmful effects. Although these results are promising, this approach is still under study, and individual experiences may vary. It is crucial to discuss potential risks and benefits with a healthcare team before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for leukemia?

Researchers are excited about the stem cell transplantation technique for leukemia because it uniquely uses selective depletion of CD45RA+ T cells to potentially reduce the risk of graft-versus-host disease (GVHD), a common complication in traditional transplants. Unlike standard treatments that might not specifically target these cells, this approach aims to enhance the safety and effectiveness of the transplant by minimizing immune reactions. Additionally, the use of G-CSF-mobilized, CD34-enriched peripheral blood stem cells is designed to improve the chances of successful engraftment, which can lead to better outcomes for patients. This innovative method holds the promise of making stem cell transplants safer and more effective for leukemia patients.

What evidence suggests that the selective depletion of CD45RA+ T cells might be an effective treatment for leukemia?

Research has shown that a special technique in stem cell transplants, which participants in this trial will receive, can help reduce the risk of Graft-Versus-Host Disease (GVHD), a common complication. In a study with 35 patients who had high-risk acute leukemia, this method lowered the severity of GVHD and aided better immune system recovery. The technique removes certain T cells, known as naïve T cells, believed to cause GVHD, while preserving the T cells that fight leukemia and infections. Other studies have found that this method helps maintain the body's ability to remember and fight infections after the transplant. These findings suggest that this approach might make stem cell transplants safer and more effective for treating leukemia. ^{1 2 3 6 7}

Who Is on the Research Team?

Marie Bleakley

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients aged 0-60 with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who are suitable for stem cell transplantation. They must have a matched donor and acceptable organ function. Exclusions include uncontrolled infections, severe heart/lung/kidney disease, previous certain transplants, pregnancy/breastfeeding without contraception use, other significant medical conditions or participation in conflicting trials.

Inclusion Criteria

I am a candidate for a stem cell transplant and have a specific type of blood cancer.

My donor is 18 or older, matches my HLA, and agrees to donate stem cells.

I have a donor match willing to donate stem cells.

Exclusion Criteria

I do not have uncontrolled infections, severe organ problems, HIV, or fall outside the weight limits.

My kidney, heart, lung, and liver functions meet the required levels.

Donors who are seropositive for certain viruses or infections, fail eligibility requirements, or donate outside of the USA

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients undergo chemotherapy and total-body radiotherapy to prepare for transplantation

10 days

Daily visits for treatment

Transplant

Patients receive allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells

1 day

Inpatient procedure

GVHD Prophylaxis

Patients receive medications to prevent graft-versus-host disease

50 days

Regular monitoring and medication administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Follow-up visits at 80-100 days, 360 days, and yearly

What Are the Treatments Tested in This Trial?

Interventions

• Selective Depletion of CD45RA+ T Cells

Trial Overview The trial tests whether selectively removing naïve T cells from donor stem cells before transplant can prevent Graft-Versus-Host-Disease (GVHD) while preserving the benefits of fighting infections and killing residual leukemia cells. It involves high/medium intensity chemo/radiotherapy followed by infusion of modified donor blood stem cells.

How Is the Trial Designed?

Group I: Arm D (MUD) Experimental Treatment 8 Interventions

LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.

Group II: Arm C (MUD) Experimental Treatment 9 Interventions

HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Group III: Arm B (MRD) Experimental Treatment 9 Interventions

LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator.

Group IV: Arm A (MRD) Experimental Treatment 9 Interventions

HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02220985?cond=%22Blastic%20Plasmacytoid%20Dendritic%20Cell%20Neoplasm%22&intr=%22anti-bacterial%20agents%22&viewType=Table&rank=4

Selective Depletion of CD45RA+ T Cells From Allogeneic ... This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9911795/

Selective depletion of naïve T cells by targeting CD45RA - PMC In their study, 35 patients with high-risk acute leukemia received these CD45RA+-depleted grafts from MSDs after myeloablative conditioning. No ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00914940

Selective Depletion of CD45RA+T Cells From Allogeneic ... PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5809307/

Selective T-cell depletion targeting CD45RA reduces viremia ... We hypothesized that specific depletion of CD45RA+ naïve T cells, rather than broad depletion of CD3+ T cells, can preserve memory-immunity in the allografts.

5. astctjournal.org astctjournal.org/article/S2666-6367(21)00753-3/fulltext

Feasibility and Efficacy of CD45RA+ Depleted Donor ... Feasibility and efficacy of CD45RA+ depleted donor lymphocytes infusion after haploidentical transplantation with post-transplantation cyclophosphamide.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12062598/

Selective TCRαβ+ and CD45RA+ T-cell depletion of ... CD45RA depletion resulted in a median 4.8 (4.3–5.2) log reduction, with CD3+/CD45RO+ cell recovery at 41% (34%–47%) and CD34 recovery at 58% (51 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022175921000053

Depletion of CD45RA + T cells: Advantages and ... Stem cell recovery after one-step CD45RA-depletion was at median 52.0% (range: 49.7–67.2%), which was comparable to previously published recovery data received ...