- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01858740
Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts in Preventing GVHD in Children
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 Overview
Status
Conditions
- Recurrent Adult Acute Myeloid Leukemia
- Adult Acute Myeloid Leukemia in Remission
- Childhood Acute Myeloid Leukemia in Remission
- Adult Acute Lymphoblastic Leukemia in Remission
- Childhood Acute Lymphoblastic Leukemia in Remission
- Recurrent Adult Acute Lymphoblastic Leukemia
- Recurrent Childhood Acute Lymphoblastic Leukemia
- Recurrent Childhood Acute Myeloid Leukemia
- Refractory Adult Acute Lymphoblastic Leukemia
- Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Myelodysplastic Syndrome With Excess Blasts-2
- Acute Leukemia of Ambiguous Lineage
- Acute Undifferentiated Leukemia
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Acute Biphenotypic Leukemia
- Refractory Childhood Acute Lymphoblastic Leukemia
- Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Myelodysplastic Syndrome With Excess Blasts-1
Intervention / Treatment
- Other: Laboratory Biomarker Analysis
- Drug: Methotrexate
- Radiation: Total-Body Irradiation
- Drug: Fludarabine Phosphate
- Drug: Tacrolimus
- Drug: Thiotepa
- Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
- Procedure: Peripheral Blood Stem Cell Transplantation
- Biological: T Cell-Depleted Hematopoietic Stem Cell Transplantation
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109
- Fred Hutch/University of Washington Cancer Consortium
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (CD45RA+ T cell depleted PBSCT)
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. |
Correlative studies
Given IV
Other Names:
Undergo TBI
Other Names:
Given IV
Other Names:
Given IV or PO
Other Names:
Given IV
Other Names:
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Other Names:
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
Other Names:
Undergo CD45RA+ T cell-depleted allogeneic peripheral blood stem cell transplant
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Graft Failure
Time Frame: Up to 5 years
|
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
|
Time to Discontinuation of Systemic Immunosuppression
Time Frame: 5 years post transplant
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Platelet Count > 50,000/uL for 3 Days Without Transfusion
Time Frame: Up to 5 years
|
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
|
Time to Platelet Count > 20,000/uL for 3 Days Without Transfusion
Time Frame: Up to 5 years
|
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
|
Time to ANC of > 1,000/uL
Time Frame: Up to 5 years
|
Time (in days) to ANC of > 1,000/uL, counted as the first of three consecutive days post-transplant
|
Up to 5 years
|
Time to ANC of > 500/uL
Time Frame: Up to 5 years
|
Time (in days) to ANC of > 500/uL, counted as the first of three consecutive days post-transplant
|
Up to 5 years
|
Occurrence of Chronic GHVD Meeting NIH Criteria and Requiring Systemic Pharmacological Immunosuppression
Time Frame: Up to 5 years
|
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
|
Acute GVHD Grade III-IV
Time Frame: Up to day 100
|
Number of patients with acute GVHD grade III-IV
|
Up to day 100
|
Acute GVHD Grades II-IV
Time Frame: Up to day 100
|
Number of patients with acute GVHD grades II-IV
|
Up to day 100
|
Steroid Refractory Acute GVHD
Time Frame: Up to day 100
|
Presence of steroid refractory acute GVHD within the first 100 days post transplant
|
Up to day 100
|
Relapse Post-transplant
Time Frame: Up to 5 years
|
Relapse defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology
|
Up to 5 years
|
Transplant Related Mortality
Time Frame: Up to 5 years
|
Transplant related mortality defined as mortality in any patient for whom there has not been a diagnosis of relapse
|
Up to 5 years
|
Use of Additional Immune Suppressive Agents to Treat Chronic GVHD
Time Frame: Up to 5 years
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marie Bleakley, Fred Hutch/University of Washington Cancer Consortium
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Anemia
- Neoplastic Processes
- Precancerous Conditions
- Cell Transformation, Neoplastic
- Carcinogenesis
- Anemia, Refractory
- Chronic Disease
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Recurrence
- Preleukemia
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Leukemia, Myeloid, Accelerated Phase
- Anemia, Refractory, with Excess of Blasts
- Leukemia, Biphenotypic, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Reproductive Control Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Calcineurin Inhibitors
- Fludarabine
- Fludarabine phosphate
- Methotrexate
- Tacrolimus
- Thiotepa
Other Study ID Numbers
- 2660.00 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- NCI-2013-00958 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- 2660
- K23CA154532 (U.S. NIH Grant/Contract)
- RG9213077 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)
- R01HL121568 (U.S. NIH Grant/Contract)
- 2P01CA018029 (U.S. NIH Grant/Contract)
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