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Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

NCT03272633

Description:

This pilot clinical trial studies the side effects of irradiated donor cells following stem cell transplant in controlling cancer in patients with hematologic malignancies. Transfusion of irradiated donor cells (immune cells) from relatives may cause the patient's cancer to decrease in size and may help control cancer in patients receiving a stem cell transplant.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Double-Hit Lymphoma
  • Mantle Cell Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies
  • Official Title: Post-Transplant Use of Irradiated Haplo-Allogeneic Cells

Clinical Trial IDs

  • ORG STUDY ID: 011702
  • SECONDARY ID: NCI-2017-01537
  • SECONDARY ID: Pro20170000537
  • SECONDARY ID: 011702
  • SECONDARY ID: P30CA072720
  • NCT ID: NCT03272633

Conditions

  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia in Remission
  • Hematopoietic Cell Transplantation Recipient
  • JAK2 Gene Mutation
  • Loss of Chromosome 17p
  • Mantle Cell Lymphoma
  • Minimal Residual Disease
  • Myelodysplastic Syndrome
  • Non-Hodgkin Lymphoma
  • Plasma Cell Myeloma
  • RAS Family Gene Mutation
  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Hematologic Malignancy
  • Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Therapy-Related Acute Myeloid Leukemia
  • Therapy-Related Myelodysplastic Syndrome
  • TP53 Gene Mutation

Interventions

DrugSynonymsArms
Irradiated Allogeneic CellsCohort I (initial IHC within 42 days)

Purpose

This pilot clinical trial studies the side effects of irradiated donor cells following stem cell transplant in controlling cancer in patients with hematologic malignancies. Transfusion of irradiated donor cells (immune cells) from relatives may cause the patient's cancer to decrease in size and may help control cancer in patients receiving a stem cell transplant.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the toxicity associated with the administration of irradiated haploidentical
      cells (IHC) to patients with high-risk hematologic malignancies.

      SECONDARY OBJECTIVES:

      I. To determine if there is evidence of disease response associated with IHC.

      TERTIARY OBJECTIVES:

      I. To determine if treatment with the irradiated cells induces an immune response targeting
      tumor associated epitopes.

      OUTLINE: Patients are assigned to 1 of 2 cohorts.

      COHORT I: Within 42 days after hematopoietic engraftment (both neutrophils and platelets)
      after autologous hematopoietic stem cell transplantation (HSCT), patients receive initial
      treatment with IHC. Patients that do not have evidence of relapse or progressive disease may
      be treated every 8-12 weeks for up to 3 doses.

      COHORT II: Patients with high-risk disease receive initial treatment with IHC within 70 days
      after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT.
      Patients being treated for relapsed disease may receive initial treatment with IHC any time
      after relapse is documented. Patients that do not have evidence of relapse or progressive
      disease may be treated every 8-12 weeks for up to 3 doses.

      After completion of study treatment, patients will be followed up within 8 weeks.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort I (initial IHC within 42 days)ExperimentalWithin 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous HSCT, patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.
    Cohort II (initial IHC within 70 days or after relapse)ExperimentalPatients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Patient with disease (stage) eligible per cohort
      
                -  COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue
                   and ?high-risk? disease as defined below:
      
                     -  Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified
                        World Health Organization [WHO] subtypes) not in computed tomography
                        (CT)-positron emission tomography (PET) complete remission at time of high dose
                        therapy
      
                     -  Diffuse large cell lymphoma with ?double hit? or ?double expressor? features
      
                     -  Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO
                        specified subtypes) refractory to standard induction therapy OR relapsing within
                        1 year of treatment OR in greater that second complete remission (CR)
      
                     -  Mantle cell lymphoma not in CR1
      
                     -  Multiple myeloma with ONE (or more) of the following high risk features:
      
                          -  Less than very good partial remission at time of high dose therapy
      
                          -  High Revised-International Staging System (R-ISS) (stage III ? 2
                             microglobulin >= 5.5 plus lactate dehydrogenase [LDH] > upper limit of
                             normal [ULN] and/or del17p, t(4;14), t(14;16)) at time of diagnosis
      
                          -  Cytogenetics or fluorescent in situ hybridization (FISH) del17p
      
                -  COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic
                   stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one
                   of the following disease subtypes:
      
                     -  Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia
                        Network [ELN]) at presentation
      
                          -  Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p,
                             complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose
                             samples have mutations in RUNX1 or ASXL1 are also eligible (unless the
                             patient has favorable cytogenetics)
      
                     -  AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g.,
                        myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding
                        factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry
      
                     -  AML not in CR1 (including patients with morphologic CR but with incomplete
                        recovery, CRi)
      
                     -  Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53
                        mutation, or JAK2 or RAS mutation
      
                     -  Treatment-related MDS or AML
      
                     -  Acute lymphoblastic leukemia (ALL) not in CR1
      
                     -  ALL with MRD
      
                     -  Any hematologic malignancy relapsed or with persistent disease after allogeneic
                        hematopoietic stem cell transplant
      
                     -  Multiple myeloma
      
                     -  Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant
      
                     -  Any patient undergoing allogeneic hematopoietic stem cell transplant and an
                        anticipated rate of relapse > 80% based upon published data and for which there
                        is consensus amongst the Hematologic Malignancies Tumor Study Group that
                        enrollment is appropriate
      
                -  Availability of a genetic child, genetic parent or sibling as a potential HLA
                   haploidentical donor
      
                -  Meets standard eligibility requirements for high dose chemotherapy with autologous
                   stem cell rescue (COHORT 1) or allogeneic hematopoietic stem cell transplant (COHORT
                   2) and has signed consent for those procedures
      
                -  DONOR: Donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched
      
                -  DONOR: Donor must meet all Robert Wood Johnson (RWJ) Blood Services requirements for
                   hematopoietic stem cell donation including:
      
                     -  Age >= 18 years old;
      
                     -  Normal hemogram (white blood cells [WBC] 4.0-10.0 x 10^3/mm^3; platelet count
                        150,000 to 440,000/mm^3 ; hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
      
                     -  Not pregnant or lactating;
      
                     -  Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV),
                        hepatitis B core or human T-cell lymphotropic virus (HTLV)-I/II seropositive;
                        hepatitis B surface antigen (HB S ag) (-); meet other infectious disease
                        screening criteria utilized by RWJ Blood Services;
      
                     -  No uncontrolled infections, other medical or psychological/social conditions, or
                        medications that might increase the likelihood of patient or donor adverse
                        effects or poor outcomes;
      
                     -  Meet other blood bank criteria for blood product donation (as determined by RWJ
                        Blood Center screening history and laboratory studies)
      
              Exclusion Criteria:
      
                -  Non-English speaking person
      
                -  Patients undergoing haploidentical allogeneic hematopoietic stem cell transplants are
                   not eligible; patients undergoing < 10/10 HLA allele matched allogeneic transplant are
                   not eligible
      
                -  Pregnant women
      
                -  DONOR: Non-English speaking person
      
                -  DONOR: Pregnant women
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Disease response in patients who receive irradiated haploidentical cells (IHC)
      Time Frame:Up to 8 weeks after last protocol treatment
      Safety Issue:
      Description:It will be determined if there is evidence of disease response to IHC. Disease response will use standard disease-specific parameters.

      Secondary Outcome Measures

      Measure:Induction of host T cells reactive with tumor associated epitopes
      Time Frame:Up to 8 weeks after last protocol treatment
      Safety Issue:
      Description:It will be determined if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Rutgers, The State University of New Jersey

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