Stem Cell Transplantation for Leukemia

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

84 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.

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+