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Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Primary Purpose

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Biphenotypic Leukemia, Acute Leukemia of Ambiguous Lineage

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Allogeneic Hematopoietic Stem Cell Transplantation

Cyclophosphamide

Fludarabine Phosphate

Laboratory Biomarker Analysis

Methotrexate

Mycophenolate Mofetil

Peripheral Blood Stem Cell Transplantation

Tacrolimus

Thiotepa

Total-Body Irradiation

About this trial

This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Eligibility Criteria

undefined - 60 Years (Child, Adult)All SexesAccepts 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 (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 < 45%
Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 60%; 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
Liver function abnormality; patients who have liver function tests (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 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 < 35%
DLCO corrected < 50%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the O2 saturation is < 92% on room air; patients with a DLCO 50-60% must also have a partial pressure of oxygen (pO2) of > 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 hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded
Patients will be excluded from Arms A and C if they have received a previous myeloablative transplant; patients who have received a prior HCT at least 6 months prior may be considered for inclusion on Arms B or D after discussion with the principal investigator (PI)
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, methotrexate (Arm A or C) or MMF (Arm B or D)
DONOR EXCLUSION:
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
Donors who fail eligibility requirements for donation of cells or tissue for donation of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells complies urgent medical need or allogeneic use in a first-degree or second-degree relative
Unrelated donors donating outside of the United States of America (USA)

Sites / Locations

University of Pittsburgh Cancer Institute (UPCI)
Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm A (MRD)

Arm B (MRD)

Arm C (MUD)

Arm D (MUD)

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression

Match related donor (MRD)-high intensity (Arm A), MRD-lower intensity (Arm B), match unrelated donor (MUD)-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.

Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine)

Time to completion of prednisone

Time to completion of all immunosuppression

Requirement of immunosuppression after transplant

Presence of acute graft-versus-host disease (GVHD) grades II-IV

Defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver.

Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management

Graft failure

Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft.

Secondary Outcome Measures

Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days

Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results

Time to platelet count > 20,000/uL for 3 days without transfusion

Time to platelet count > 50,000/uL for 3 days without transfusion

Chimerism analysis

Will be analyzed from peripheral blood or marrow.

Relapse

Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.

Transplant related mortality

Defined as mortality in any patient for whom there has not been a diagnosis of relapse.

Full Information

NCT ID

NCT02220985

First Posted

August 18, 2014

Last Updated

August 7, 2023

Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT02220985

Brief Title

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Official Title

A Phase II Study Evaluating Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors for Prevention of GVHD

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 3, 2015 (Actual)

Primary Completion Date

April 1, 2025 (Anticipated)

Study Completion Date

April 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fred Hutchinson Cancer Center

Collaborators

National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed Description

OUTLINE: Patients are assigned to 1 of 4 treatment arms. CONDITIONING: ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. ARMS B AND D (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 once daily (QD) on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally (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. ARMS B AND D: 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 days -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. After completion of study treatment, patients are followed up at 80-100 days, 360 days, and then yearly for up to 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Blastic Plasmacytoid Dendritic Cell Neoplasm, Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Myeloid Leukemia in Remission, Donor, Lymphoblastic Lymphoma, Myelodysplastic Syndrome With Excess Blasts, Myelodysplastic Syndrome With Excess Blasts-1, Myelodysplastic Syndrome With Excess Blasts-2, Recurrent Acute Lymphoblastic Leukemia, Recurrent Acute Myeloid Leukemia, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Refractory Acute Lymphoblastic Leukemia, Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia in Remission

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

84 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A (MRD)

Arm Type

Experimental

Arm Description

Arm Title

Arm B (MRD)

Arm Type

Experimental

Arm Description

Arm Title

Arm C (MUD)

Arm Type

Experimental

Arm Description

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.

Arm Title

Arm D (MUD)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Procedure

Intervention Name(s)

Allogeneic Hematopoietic Stem Cell Transplantation

Other Intervention Name(s)

Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Intervention Description

Undergo allogeneic HSCT

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Fludarabine Phosphate

Other Intervention Name(s)

2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Intervention Description

Given IV

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Mycophenolate Mofetil

Other Intervention Name(s)

Cellcept, MMF

Intervention Description

Given IV and PO

Intervention Type

Procedure

Intervention Name(s)

Peripheral Blood Stem Cell Transplantation

Other Intervention Name(s)

PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Intervention Description

Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC

Intervention Type

Procedure

Intervention Name(s)

Peripheral Blood Stem Cell Transplantation

Other Intervention Name(s)

PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Intervention Description

Undergo PBSCT with CD45RA-depleted cells

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Other Intervention Name(s)

FK 506, Fujimycin, Hecoria, Prograf, Protopic

Intervention Description

Given IV or PO

Intervention Type

Drug

Intervention Name(s)

Thiotepa

Other Intervention Name(s)

1,1',1''-Phosphinothioylidynetrisaziridine, Girostan, N,N', N''-Triethylenethiophosphoramide, Oncotiotepa, STEPA, Tepadina, TESPA, Tespamin, Tespamine, Thio-Tepa, Thiofosfamide, Thiofozil, Thiophosphamide, Thiophosphoramide, Thiotef, Tifosyl, TIO TEF, Tio-tef, Triethylene thiophosphoramide, Triethylenethiophosphoramide, Tris(1-aziridinyl)phosphine sulfide, TSPA, WR 45312

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Total-Body Irradiation

Other Intervention Name(s)

Total Body Irradiation, Whole-Body Irradiation, TBI, Whole Body Irradiation

Intervention Description

Undergo TBI

Primary Outcome Measure Information:

Title

Description

Match related donor (MRD)-high intensity (Arm A), MRD-lower intensity (Arm B), match unrelated donor (MUD)-high intensity (Arm C) and MUD-lower intensity (Arm D) cohorts will be analyzed separately.

Time Frame

Up to 5 years

Title

Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine)

Time Frame

Up to 5 years

Title

Time to completion of prednisone

Time Frame

Up to 5 years

Title

Time to completion of all immunosuppression

Time Frame

Up to 5 years

Title

Requirement of immunosuppression after transplant

Time Frame

At 2 years after transplant

Title

Presence of acute graft-versus-host disease (GVHD) grades II-IV

Description

Defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver.

Time Frame

Up to day 100

Title

Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management

Time Frame

Up to day 100

Title

Graft failure

Description

Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft.

Time Frame

Up to day 28

Secondary Outcome Measure Information:

Title

Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days

Time Frame

Up to 5 years

Title

Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results

Time Frame

Up to 5 years

Title

Time to platelet count > 20,000/uL for 3 days without transfusion

Time Frame

Up to 5 years

Title

Time to platelet count > 50,000/uL for 3 days without transfusion

Time Frame

Up to 5 years

Title

Chimerism analysis

Description

Will be analyzed from peripheral blood or marrow.

Time Frame

Up to 360 days

Title

Relapse

Description

Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology.

Time Frame

Up to 5 years

Title

Transplant related mortality

Description

Defined as mortality in any patient for whom there has not been a diagnosis of relapse.

Time Frame

Up to 5 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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 < 45% Diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 60%; 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 Liver function abnormality; patients who have liver function tests (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 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 < 35% DLCO corrected < 50%; patients who are unable to perform pulmonary function tests (for example, due to young age and/or developmental status) will be excluded if the O2 saturation is < 92% on room air; patients with a DLCO 50-60% must also have a partial pressure of oxygen (pO2) of > 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 hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease will be excluded Patients will be excluded from Arms A and C if they have received a previous myeloablative transplant; patients who have received a prior HCT at least 6 months prior may be considered for inclusion on Arms B or D after discussion with the principal investigator (PI) 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, methotrexate (Arm A or C) or MMF (Arm B or D) DONOR EXCLUSION: 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 Donors who fail eligibility requirements for donation of cells or tissue for donation of a Human Cell and Tissue Products (HCT/P) will be excluded unless use of the cells complies urgent medical need or allogeneic use in a first-degree or second-degree relative Unrelated donors donating outside of the United States of America (USA)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marie Bleakley

Organizational Affiliation

Fred Hutch/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pittsburgh Cancer Institute (UPCI)

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

Facility Name

Fred Hutch/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

35007144

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.

Results Reference

derived

Learn more about this trial

Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

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