Clinical trial NCT01858740: Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children
Official title: A Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD in Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Acute Biphenotypic Leukemia
Acute Leukemia of Ambiguous Lineage
Acute Undifferentiated Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Chronic Myelogenous Leukemia, BCR-ABL1 Positive
Myelodysplastic Syndrome With Excess Blasts-1
Myelodysplastic Syndrome With Excess Blasts-2
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Refractory Adult Acute Lymphoblastic Leukemia
Refractory Childhood Acute Lymphoblastic Leukemia
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2013-05-21
Enrollment: 20
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well T cell depleted donor peripheral blood stem cell transplant works in preventing graft-versus-host disease in younger patients with high risk hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Removing a subset of the T cells from the donor cells before transplant may stop this from happening.

Detailed description: OUTLINE:

CONDITIONING REGIMEN: Patients undergo total body irradiation (TBI) twice daily (BID) on days -10 to -7, receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.

TRANSPLANT: Patients undergo CD34+ enriched, CD45RA+ T cell-depleted allogeneic PBSCT on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and continuing through day 50 with taper. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed up for up to 5 years.

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
  * Acute myeloid leukemia in relapse or primary refractory disease with a circulating blast count of no more than 10,000/mm\^3
  * Refractory anemia with excess blasts (RAEB-1 and RAEB-2)
  * Chronic myelogenous leukemia with a history of accelerated phase or blast crisis
  * Other acute leukemia (including but not limited to 'biphenotypic', 'undifferentiated' or 'ambiguous lineage' acute leukemia)
* Patient with a human leukocyte antigen (HLA)-identical (HLA-A, B, C, and ribonucleic acid \[RNA\] binding motif protein 45 \[DRB1\] molecularly matched) unrelated donor or related donor capable of donating PBSC
* DONOR: HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC
* DONOR: HLA-matched related donors \>= 18 years and capable and willing to donate PBSC

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
* Patients who weigh \>= 70 kg must be discussed with the principal investigator prior to enrolling on the protocol
* Patients who are human immunodeficiency virus positive (HIV+)
* Patients with uncontrolled infections for whom myeloablative hematopoietic stem cell transplant (HCT) is considered contraindicated by the consulting infectious disease physician (upper respiratory tract viral infection does not constitute an uncontrolled infection in this context)
* Creatinine \> 1.5 mg/dl
* Cardiac ejection fraction \< 45%
* Patients who can perform pulmonary function tests will be excluded if they have a diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) of \< 60% predicted; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the oxygen (O2) saturation is \< 92% on room air
* Patients who have liver function test (LFTs) (including total bilirubin, aspartate aminotransferase \[AST\] and alanine aminotransferase \[ALT\]) \>= 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 protocol 2660 is contraindicated for that patient the patient will be 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 protocol
* Patients with a life expectancy \< 3 months from co-existing disease other than the leukemia or RAEB
* Patients who are pregnant or breast-feeding
* Fertile patients of child bearing age unwilling to use contraception during and for 12 months post-transplant
* Patients with a significant other medical conditions that would make them unsuitable for transplant
* Patients with a known hypersensitivity to tacrolimus
* DONOR: Donors who are HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
* DONOR: Donors who fail eligibility requirements for donation of cells or tissue per section 21 Code of Federal Regulations (CFR) 1271 for donation of a HCT/product (P) will be excluded unless use of the cells complies with 21 CFR 1271.65(b)(iii) (urgent medical need) or with 21 CFR 1271.65(b)(i) (allogeneic use in a first-degree or second-degree relative)
* DONOR: Unrelated donors donating outside of the United States of America (USA) or Germany

Primary outcomes:
measure: Graft Failure
timeFrame: Up to 5 years
measure: Time to Discontinuation of Systemic Immunosuppression
timeFrame: 5 years post transplant
Secondary outcomes:
measure: Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion
timeFrame: Up to 5 years
measure: Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion
timeFrame: Up to 5 years
measure: Time to ANC of > 1,000/uL
timeFrame: Up to 5 years
measure: Time to ANC of > 500/uL
timeFrame: Up to 5 years
measure: Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression
timeFrame: Up to 5 years
measure: Acute GVHD Grade III-IV
timeFrame: Up to day 100
measure: Acute GVHD Grades II-IV
timeFrame: Up to day 100
measure: Steroid Refractory Acute GVHD
timeFrame: Up to day 100
measure: Relapse Post-transplant
timeFrame: Up to 5 years
measure: Transplant Related Mortality
timeFrame: Up to 5 years
measure: Use of Additional Immune Suppressive Agents to Treat Chronic GVHD
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Marie Bleakley
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10.