Clinical Trials /

Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

NCT02960646

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Aplastic Anemia
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Hodgkin Lymphoma
  • Lymphoblastic Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
  • Therapy-Related Chronic Myelomonocytic Leukemia
  • Therapy-Related Myelodysplastic Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2014-0738
  • SECONDARY ID: NCI-2016-01915
  • SECONDARY ID: 2014-0738
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02960646

Conditions

  • 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

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-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- 138719Treatment (peripheral blood stem cell transplantation)
FilgrastimFILGRASTIM, LICENSE HOLDER UNSPECIFIED, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, TevagrastimTreatment (peripheral blood stem cell transplantation)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment (peripheral blood stem cell transplantation)
MelphalanAlanine 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-19813Treatment (peripheral blood stem cell transplantation)
RituximabABP 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, RTXM83Treatment (peripheral blood stem cell transplantation)
TacrolimusFK 506, Fujimycin, Hecoria, Prograf, ProtopicTreatment (peripheral blood stem cell transplantation)

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (peripheral blood stem cell transplantation)ExperimentalPatients 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.
  • Cyclophosphamide
  • Filgrastim
  • Fludarabine Phosphate
  • Melphalan
  • Rituximab
  • Tacrolimus

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
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Immune reconstitution
Time Frame:Up to 3 years
Safety Issue:
Description:Will be summarized by number of participants.
Measure:Incidence of infectious episodes
Time Frame:Up to 3 years
Safety Issue:
Description:Will be summarized by number of participants.
Measure:Disease free survival (DFS) time
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Overall survival (OS) time
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

January 3, 2020