Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT ID: NCT02960646

Last Updated: 2023-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-01-18

Study Completion Date

2023-02-13

Brief Summary

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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

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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.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (peripheral blood stem cell transplantation)

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.

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given IV

Filgrastim

Intervention Type BIOLOGICAL

Given SC

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Melphalan

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo CD45RA depleted peripheral blood stem cell transplantation

Rituximab

Intervention Type BIOLOGICAL

Given IV

Tacrolimus

Intervention Type DRUG

Given IV or PO

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Interventions

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Cyclophosphamide

Given IV

Intervention Type DRUG

Filgrastim

Given SC

Intervention Type BIOLOGICAL

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Melphalan

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo CD45RA depleted peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Rituximab

Given IV

Intervention Type BIOLOGICAL

Tacrolimus

Given IV or PO

Intervention Type DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Other Intervention Names

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(-)-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 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 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 PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation 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 FK 506 Fujimycin Hecoria Prograf Protopic TBI Total Body Irradiation Whole Body Irradiation Whole-Body Irradiation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Samer Srour

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

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NCI-2016-01915

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-0738

Identifier Type: OTHER

Identifier Source: secondary_id

2014-0738

Identifier Type: -

Identifier Source: org_study_id

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