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Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT02960646
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Acute Myeloid Leukemia in Remission Adult Acute Lymphoblastic Leukemia in Complete Remission Aplastic Anemia Blasts Under 10 Percent of Bone Marrow Nucleated Cells Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Hematopoietic Cell Transplantation Recipient Minimal Residual Disease Myeloproliferative Neoplasm Plasma Cell Myeloma Recurrent Chronic Lymphocytic Leukemia Recurrent Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Recurrent Plasma Cell Myeloma Recurrent Small Lymphocytic Lymphoma Therapy-Related Myelodysplastic Syndrome Drug: Cyclophosphamide Biological: Filgrastim Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Drug: Melphalan Procedure: Peripheral Blood Stem Cell Transplantation Biological: Rituximab Drug: Tacrolimus Radiation: Total-Body Irradiation Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation
Actual Study Start Date : January 18, 2017
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2020


Arm Intervention/treatment
Experimental: 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 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 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.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Biological: Filgrastim
Given SC
Other Names:
  • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tevagrastim

Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Melphalan
Given IV
Other Names:
  • 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

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo CD45RA depleted peripheral blood stem cell transplantation
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Biological: Rituximab
Given IV
Other Names:
  • 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 Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Tacrolimus
Given IV or PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Total Body Irradiation
  • Whole-Body Irradiation




Primary Outcome Measures :
  1. 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 Measures :
  1. Immune reconstitution [ Time Frame: Up to 3 years ]
    Will be summarized by number of participants.

  2. Incidence of infectious episodes [ Time Frame: Up to 3 years ]
    Will be summarized by number of participants.

  3. Disease free survival (DFS) time [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan and Meier.

  4. Overall survival (OS) time [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan and Meier.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02960646


Contacts
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Contact: Stefan Ciurea 713-792-8750 sciurea@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Stefan O. Ciurea    713-792-8750      
Principal Investigator: Stefan O. Ciurea         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stefan O Ciurea M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02960646     History of Changes
Other Study ID Numbers: 2014-0738
NCI-2016-01915 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0738 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: July 10, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Aplastic
Anemia
Lymphoma
Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasm, Residual
Myelodysplastic Syndromes
Myeloproliferative Disorders
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease
Pathologic Processes
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias