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

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Completed

Phase 2

Conditions

Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Acute Biphenotypic Leukemia

Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Acute Leukemia of Ambiguous Lineage

Myelodysplastic Syndrome With Excess Blasts-1

Childhood Acute Myeloid Leukemia in Remission

Recurrent Childhood Acute Lymphoblastic Leukemia

Adult Acute Myeloid Leukemia in Remission

Refractory Adult Acute Lymphoblastic Leukemia

Adult Acute Lymphoblastic Leukemia in Remission

Myelodysplastic Syndrome With Excess Blasts-2

Refractory Childhood Acute Lymphoblastic Leukemia

Childhood Acute Lymphoblastic Leukemia in Remission

Recurrent Childhood Acute Myeloid Leukemia

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Adult Acute Myeloid Leukemia

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Acute Undifferentiated Leukemia

Treatments

Drug: Thiotepa

Drug: Methotrexate

Other: Laboratory Biomarker Analysis

Radiation: Total-Body Irradiation

Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation

Drug: Fludarabine Phosphate

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Drug: Tacrolimus

Procedure: Peripheral Blood Stem Cell Transplantation

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01858740

K23CA154532 (U.S. NIH Grant/Contract)

NCI-2013-00958 (Registry Identifier)

RG9213077 (Other Identifier)

2P01CA018029 (U.S. NIH Grant/Contract)

2660.00 (Other Identifier)

R01HL121568 (U.S. NIH Grant/Contract)

2660

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

20 participants in 1 patient group

Treatment (CD45RA+ T cell depleted PBSCT)

Experimental group

Description:

CONDITIONING REGIMEN: Patients undergo TBI BID on days -10 to -7, receive thiotepa 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 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.

Treatment: