Phase 2
N=77
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive · Acute Biphenotypic Leukemia · Acute Leukemia of Ambiguous Lineage · Acute Undifferentiated Leukemia · Allogeneic Hematopoietic Stem Cell Transplant Recipient
Bottom Line
View on ClinicalTrials.gov: NCT02220985 ↗Enrolled (actual)
77
Serious AEs
92.2%
Results posted
Jun 2026
Primary outcome: Primary: Chronic GVHD — 17; 20; 14; 17 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Allogeneic Hematopoietic Stem Cell Transplantation (Procedure); Cyclophosphamide (Drug); Fludarabine Phosphate (Drug); Laboratory Biomarker Analysis (Other); Methotrexate (Drug); Mycophenolate Mofetil (Drug); Peripheral Blood Stem Cell Transplantation (Procedure); Tacrolimus (Drug); Thiotepa (Drug); Total-Body Irradiation (Radiation)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- Fred Hutchinson Cancer Center
- Primary completion
- Apr 2025
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Chronic GVHD |
17; 20; 14; 17; 3; 0 | — |
| PRIMARY Time to Completion of Prednisone |
65; 68; 87; 79 | — |
| PRIMARY Time to Completion of All Immunosuppression |
252; 216; 244; 223 | — |
| PRIMARY Requirement of Immunosuppression at 2 Years After Transplant |
0; 1; 0; 1 | — |
| PRIMARY Acute GVHD |
5; 5; 4; 3; 15; 14 | — |
| PRIMARY Graft Failure |
0; 0; 0; 0 | — |
| SECONDARY Transplant Related Mortality by Day 100 |
1; 0; 1; 0 | — |
| SECONDARY Relapse |
3; 9; 4; 4 | — |
Summary
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.
Eligibility Criteria
Inclusion Criteria
- Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
- Acute lymphocytic leukemia in first or subsequent remission
- Acute myeloid leukemia in first or subsequent remission
- Acute lymphocytic leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)
- Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm^3 (Arms A or C only)
- Refractory anemia with excess blasts (RAEB-1 and RAEB-2) (if the patient has received previous induction chemotherapy within 60 days)
- Chronic myelogenous leukemia with a history of accelerated phase or blast crisis (if the patient has received at least one course of induction chemotherapy)
- Other acute leukemia or related neoplasm (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia, blastic plasmacytoid dendritic cell neoplasm or lymphoblastic lymphoma)
- Patients 0-49 years old will be enrolled in Arm A or C (high-intensity)
- Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator
- Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC
- DONOR INCLUSION:
- HLA-matched related donors >= 18 years and capable and willing to donate PBSC (Arms A and B)
- HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC (Arms C and D)
Exclusion Criteria
- Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy and/or standard cranial-spinal radiation
- Patients on other experimental protocols for prevention of acute GVHD
- Patient weight >= 100 kg; patients >= 70 kg with MUDs must be discussed with the principal investigator
- Patients who are human immunodeficiency virus positive (HIV+)
- Patients with uncontrolled infections for whom myeloablative HCT is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)
- Patients with organ dysfunction
- ARM A OR C EXCLUSION:
- Creatinine > 1.5 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance of > 40 ml/min
- Cardiac ejection fraction = twice the upper limit of normal should be evaluated by a gastrointestinal (GI) physician; unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); if the GI physician considers that HCT on the high-intensity arms of protocol is contraindicated for that patient the patient may be considered for treatment on the lower intensity arm of the protocol or excluded from the protocol; patients with Gilbert's syndrome and no other known liver function abnormality and patients with reversible drug-related transaminitis do not necessarily require GI consultation and may be included on the high-intensity arms of the protocol
- ARM B OR D EXCLUSION:
- Creatinine > 2.0 mg/dl at the present time; patients with a known history of creatinine > 1.5 mg/dl must have a current estimated creatinine clearance > 40 ml/min
- Cardiac ejection fraction 80 mmHg
- Liver function abnormality; patients who have LFTs >= twice the upper limit of normal should be evaluated by a GI physician unless there is a clear precipitating factor (such as an azole, methotrexate, Bactrim or another drug); patients with fulminant liver failure, cirrhosis with evidence of portal hyperten
Data sourced from ClinicalTrials.gov (NCT02220985). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.