Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Primary Purpose
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Filgrastim
Fludarabine Phosphate
Laboratory Biomarker Analysis
Melphalan
Peripheral Blood Stem Cell Transplantation
Rituximab
Tacrolimus
Total-Body Irradiation
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Lack of a human leukocyte antigen (HLA) matched related donor, lack of an immediately available 8/8 HLA matched unrelated donor
- Patients must be diagnosed with a high-risk and/or advanced hematologic malignancy defined as one of the following
- Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high-risk features including adverse cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
- Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than 1 cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem duplications, DNMT3a, TET2, MLL-partial tandem duplication (PTD), ASXL1, PHF6; FAB M6 or M7 classification; adverse cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8, complex (> 3 abnormalities)
- Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute peripheral blood blast count
- Patients with AML in CR2, subsequent CR or with active disease at transplant (< 10% bone marrow blasts)
- MDS with International Prognostic Scoring System (IPSS) intermediate-2 or higher, therapy-related MDS or chronic myelomonocytic leukemia (CMML)
- Aplastic anemia with absolute neutrophil count (ANC) < 1,000 and transfusion dependent after failed immunosuppression therapy
- Chronic myeloid leukemia (CML) >= 1st chronic phase, after failed >=2 lines of tyrosine kinase inhibitors; patients who progressed to blast phase must be in morphologic remission at transplant
- Relapsed Hodgkin's disease or non-Hodgkin's lymphoma (NHL)
- Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens with < 25% involvement by CLL/SLL cells
- Patients with lymphoblastic lymphoma in remission or after partial response to chemotherapy
- Patients with poor prognosis multiple myeloma by cytogenetics del13, del 17p, t(4;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and /or relapsed after autologous stem cell transplant
- Zubrod performance status 0-1 or Karnofsky performance status > 70%; patients > 50 years will have to have a Sorror Comorbidity Index =< 3
- Available haploidentical donor willing and eligible to undergo a peripheral blood collection
- Left ventricular ejection fraction (LVEF) > 40%
- Bilirubin =< 1.5 mg/dl (unless Gilbert's syndrome), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 200 IU/ml for adults; conjugated (direct) bilirubin < 2 x upper limit of normal
- Serum creatinine clearance >= 50 ml/min (calculated with Cockcroft-Gault formula)
- Diffusing capacity for carbon monoxide (DLCO) >= 45% predicted corrected for hemoglobin
- Patient or patient's legal representative must provide written informed consent
Exclusion Criteria:
- Human immunodeficiency virus (HIV) positive; active hepatitis B or C
- Patients with active infections; the principal investigator (PI) is the final arbiter of the eligibility
- Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
- Uncontrolled central nervous system (CNS) involvement by tumor cells within the past 2 months
- History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear)
- Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
- Inability to comply with medical therapy or follow-up
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (peripheral blood stem cell transplantation)
Arm Description
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
Outcomes
Primary Outcome Measures
Incidence of treatment failure defined as primary graft failure, grade 3-4 acute graft versus host disease (aGVHD), or non-relapse mortality
Secondary Outcome Measures
Immune reconstitution
Will be summarized by number of participants.
Incidence of infectious episodes
Will be summarized by counts of participants .
Disease free survival (DFS) time
Will be estimated using the method of Kaplan and Meier.
Overall survival (OS) time
Will be estimated using the method of Kaplan and Meier.
Full Information
NCT ID
NCT02960646
First Posted
November 8, 2016
Last Updated
February 15, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02960646
Brief Title
Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official Title
Phase I Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
January 18, 2017 (Actual)
Primary Completion Date
February 13, 2023 (Actual)
Study Completion Date
February 13, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This pilot phase I trial studies the side effects of engineered donor stem cell transplant in treating patients with hematologic malignancies. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Using T cells specially selected from donor blood in the laboratory for transplant may stop this from happening.
Detailed Description
PRIMARY OBJECTIVE:
I. To assess the safety of a modified peripheral blood (PB) graft for haploidentical transplantation, obtained by using depletion of naive, cluster of differentiation (CD)45RA+ T cells.
SECONDARY OBJECTIVES:
I. To estimate the proportion of patients with engraftment/graft failure. II. To determine the day 100 and 6 month non-relapse mortality (NRM). III. To estimate the cumulative incidence of grade 2-4 and 3-4 acute graft versus (vs.) host disease (aGVHD).
IV. To assess the rate of chronic GVHD within the first year post transplantation.
V. To assess immune reconstitution and the incidence of infectious episodes. VI. To assess disease response, disease-free survival (DFS) and overall survival (OS) after transplantation.
VII. To compare results with a retrospective cohort of patients treated with bone marrow graft on protocol 2009-0266.
OUTLINE:
Patients receive melphalan intravenously (IV) over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo total-body irradiation (TBI) on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and orally (PO) for at least 4 months. Beginning on day 7, patients receive filgrastim subcutaneously (SC) daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
After completion of study treatment, patients are followed up periodically.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Aplastic Anemia, Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelomonocytic Leukemia, Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Lymphoblastic Lymphoma, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Plasma Cell Myeloma, Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Recurrent Hodgkin Lymphoma, Recurrent Non-Hodgkin Lymphoma, Recurrent Plasma Cell Myeloma, Therapy-Related Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (peripheral blood stem cell transplantation)
Arm Type
Experimental
Arm Description
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
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, Cyclophosphamide 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
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tevagrastim
Intervention Description
Given SC
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)
Melphalan
Other Intervention Name(s)
Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813
Intervention Description
Given IV
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 CD45RA depleted peripheral blood stem cell transplantation
Intervention Type
Biological
Intervention Name(s)
Rituximab
Other Intervention Name(s)
ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima
Intervention Description
Given IV
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
Radiation
Intervention Name(s)
Total-Body Irradiation
Other Intervention Name(s)
TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation
Intervention Description
Undergo TBI
Primary Outcome Measure Information:
Title
Incidence of treatment failure defined as primary graft failure, grade 3-4 acute graft versus host disease (aGVHD), or non-relapse mortality
Time Frame
Up to 100 days
Secondary Outcome Measure Information:
Title
Immune reconstitution
Description
Will be summarized by number of participants.
Time Frame
Up to 3 years
Title
Incidence of infectious episodes
Description
Will be summarized by counts of participants .
Time Frame
Up to 3 years
Title
Disease free survival (DFS) time
Description
Will be estimated using the method of Kaplan and Meier.
Time Frame
Up to 3 years
Title
Overall survival (OS) time
Description
Will be estimated using the method of Kaplan and Meier.
Time Frame
Up to 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Lack of a human leukocyte antigen (HLA) matched related donor, lack of an immediately available 8/8 HLA matched unrelated donor
Patients must be diagnosed with a high-risk and/or advanced hematologic malignancy defined as one of the following
Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high-risk features including adverse cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than 1 cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem duplications, DNMT3a, TET2, MLL-partial tandem duplication (PTD), ASXL1, PHF6; FAB M6 or M7 classification; adverse cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8, complex (> 3 abnormalities)
Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute peripheral blood blast count
Patients with AML in CR2, subsequent CR or with active disease at transplant (< 10% bone marrow blasts)
MDS with International Prognostic Scoring System (IPSS) intermediate-2 or higher, therapy-related MDS or chronic myelomonocytic leukemia (CMML)
Aplastic anemia with absolute neutrophil count (ANC) < 1,000 and transfusion dependent after failed immunosuppression therapy
Chronic myeloid leukemia (CML) >= 1st chronic phase, after failed >=2 lines of tyrosine kinase inhibitors; patients who progressed to blast phase must be in morphologic remission at transplant
Relapsed Hodgkin's disease or non-Hodgkin's lymphoma (NHL)
Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens with < 25% involvement by CLL/SLL cells
Patients with lymphoblastic lymphoma in remission or after partial response to chemotherapy
Patients with poor prognosis multiple myeloma by cytogenetics del13, del 17p, t(4;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and /or relapsed after autologous stem cell transplant
Zubrod performance status 0-1 or Karnofsky performance status > 70%; patients > 50 years will have to have a Sorror Comorbidity Index =< 3
Available haploidentical donor willing and eligible to undergo a peripheral blood collection
Left ventricular ejection fraction (LVEF) > 40%
Bilirubin =< 1.5 mg/dl (unless Gilbert's syndrome), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 200 IU/ml for adults; conjugated (direct) bilirubin < 2 x upper limit of normal
Serum creatinine clearance >= 50 ml/min (calculated with Cockcroft-Gault formula)
Diffusing capacity for carbon monoxide (DLCO) >= 45% predicted corrected for hemoglobin
Patient or patient's legal representative must provide written informed consent
Exclusion Criteria:
Human immunodeficiency virus (HIV) positive; active hepatitis B or C
Patients with active infections; the principal investigator (PI) is the final arbiter of the eligibility
Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
Uncontrolled central nervous system (CNS) involvement by tumor cells within the past 2 months
History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear)
Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
Inability to comply with medical therapy or follow-up
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samer Srour
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
University of Texas MD Anderson Cancer Center Website
Learn more about this trial
Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
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