Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01858740
• Other study ID #: 2660.00
• Secondary ID: NCI-2013-0095826
• Status: Completed
• Phase: Phase 2
• Start date: April 10, 2014
• Est. completion date: July 30, 2023

Study information

• Verified date: March 2024
• Source: Fred Hutchinson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 30, 2023
• Est. primary completion date: January 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• 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
• Anemia, Refractory, with Excess of Blasts
• Blast Crisis
• 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
• Leukemia
• Leukemia, Biphenotypic, Acute
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome With Excess Blasts-1
• Myelodysplastic Syndrome With Excess Blasts-2
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Recurrence
• 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
• Syndrome

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Drug:
• Fludarabine Phosphate
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Methotrexate
Given IV

Procedure:
• Peripheral Blood Stem Cell Transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Biological:
• T Cell-Depleted Hematopoietic Stem Cell Transplantation
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant

Drug:
• Tacrolimus
Given IV or PO
• Thiotepa
Given IV

Radiation:
• Total-Body Irradiation
Undergo TBI

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center	National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Graft Failure	Graft failure defined as failure to reach ANC of >500/uL for 3 consecutive days by day 28, or irreversible decrease in ANC to <100 after an established donor graft. A reduction in ANC as result of relapse is not considered graft failure	Up to 5 years
Primary	Time to Discontinuation of Systemic Immunosuppression	Measure the number of days to discontinuation of systemic immunosuppression (both including and excluding calcineurin inhibitors) in pediatric recipients of CD45RA+ T cell-depleted PBSCT. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome)	5 years post transplant
Secondary	Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion	Number of days post-transplant without transfusion where platelet count is >50,000/uL. Measured as the first of three days	Up to 5 years
Secondary	Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion	Number of days post transplant until platelet count is >20,000/uL for three consecutive days without transfusion, counted as the first of three days	Up to 5 years
Secondary	Time to ANC of > 1,000/uL	Time (in days) to ANC of > 1,000/uL, counted as the first of three consecutive days post-transplant	Up to 5 years
Secondary	Time to ANC of > 500/uL	Time (in days) to ANC of > 500/uL, counted as the first of three consecutive days post-transplant	Up to 5 years
Secondary	Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression	Number of patients with chronic GVHD defined using NIH criteria. Incidents requiring only calcineurin inhibitors will not be counted. If patients do not develop cGVHD after transplant but then relapse and then receive a donor lymphocyte infusion or antigen specific T cells as treatment, they will no longer be evaluable for the cGVHD endpoint.	Up to 5 years
Secondary	Acute GVHD Grade III-IV	Number of patients with acute GVHD grade III-IV	Up to day 100
Secondary	Acute GVHD Grades II-IV	Number of patients with acute GVHD grades II-IV	Up to day 100
Secondary	Steroid Refractory Acute GVHD	Presence of steroid refractory acute GVHD within the first 100 days post transplant	Up to day 100
Secondary	Relapse Post-transplant	Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology	Up to 5 years
Secondary	Transplant Related Mortality	Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse	Up to 5 years
Secondary	Use of Additional Immune Suppressive Agents to Treat Chronic GVHD	Use of additional immune suppressive agents to treat chronic GVHD other than first line therapy. First line therapy is considered prednisone and tacrolimus/cyclosporin.	Up to 5 years