Clinical Trials /

NK Cells in Cord Blood Transplantation

NCT01619761

Description:

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Related Conditions:
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Double-Hit Lymphoma
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NK Cells in Cord Blood Transplantation
  • Official Title: Natural Killer Cells in Allogeneic Cord Blood Transplantation

Clinical Trial IDs

  • ORG STUDY ID: 2011-0493
  • SECONDARY ID: NCI-2012-02071
  • SECONDARY ID: 2011-0493
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01619761

Conditions

  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Acute Biphenotypic Leukemia
  • Acute Lymphoblastic Leukemia in Remission
  • Acute Myeloid Leukemia in Remission
  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • DS Stage II Plasma Cell Myeloma
  • DS Stage III Plasma Cell Myeloma
  • High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
  • ISS Stage II Plasma Cell Myeloma
  • ISS Stage III Plasma Cell Myeloma
  • Myelodysplastic Syndrome
  • Recurrent Acute Lymphoblastic Leukemia
  • Recurrent Acute Myeloid Leukemia
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Hodgkin Lymphoma
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Hodgkin Lymphoma
  • Refractory Non-Hodgkin Lymphoma
  • Refractory Small Lymphocytic Lymphoma
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia
  • 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 Plan 2 (NK cells, umbilical cord blood transplant)
Fludarabine Phosphate2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586Treatment Plan 1 (NK cells, umbilical cord blood transplant)
LenalidomideCC-5013, CC5013, CDC 501, RevlimidTreatment Plan 1 (NK cells, umbilical cord blood transplant)
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 Plan 1 (NK cells, umbilical cord blood transplant)
Mycophenolate MofetilCellcept, MMFTreatment Plan 1 (NK cells, umbilical cord blood transplant)
Natural Killer Cell TherapyTreatment Plan 1 (NK cells, umbilical cord blood transplant)
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 Plan 1 (NK cells, umbilical cord blood transplant)
TacrolimusFK 506, Fujimycin, Hecoria, Prograf, ProtopicTreatment Plan 1 (NK cells, umbilical cord blood transplant)

Purpose

This phase I trial studies the side effects and best way to give natural killer cells and donor umbilical cord blood transplant in treating patients with hematological malignancies. Giving chemotherapy with or without total body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the feasibility and safety of ex-vivo expanded cord blood (CB) natural killer
      (NK) cells with double CB transplantation in patients with hematological malignancies.

      SECONDARY OBJECTIVES:

      I. To monitor engraftment, chimerism, graft versus host disease, and immune reconstitution in
      patients receiving expanded CB NK cell therapy.

      II. To estimate the time to platelet recovery and the time to absolute neutrophil count (ANC)
      recovery.

      III. To estimate overall survival and disease free survival at one year. IV. To study the
      in-vivo persistence of cord blood NK cells.

      OUTLINE:

      PREPARATIVE REGIMEN: Patients are assigned to 1 of 2 treatment plans:

      TREATMENT PLAN 1: Patients receive high-dose lenalidomide orally (PO) once daily (QD) on days
      -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30
      minutes on day -4. CD20 positive patients also receive rituximab intravenously (IV) over 6
      hours on days -8 to -4.

      TREATMENT PLAN 2: Patients receive high-dose lenalidomide PO QD on days -7 to -2,
      cyclophosphamide IV over 3 hours on day -7, and undergo total body irradiation (TBI) on day
      -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.

      NK CELL INFUSION: All patients receive ex-vivo expanded cord blood NK cells IV over 30
      minutes on day -2.

      TRANSPLANT: All patients undergo allogeneic umbilical cord blood transplant on day 0.

      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: All patients receive tacrolimus IV or PO on
      days -2 to 180 followed by taper and mycophenolate mofetil IV over 2 hours or PO thrice daily
      (TID) on days -3 to 100.

      After completion of study treatment, patients are followed up at 3, 6, and 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment Plan 1 (NK cells, umbilical cord blood transplant)ExperimentalPatients receive high-dose lenalidomide PO QD on days -8 to -2, fludarabine phosphate IV over 1 hour on days -7 to -4, and melphalan IV over 30 minutes on day -4. CD20 positive patients also receive rituximab IV over 6 hours on days -8 to -4.
  • Fludarabine Phosphate
  • Lenalidomide
  • Melphalan
  • Mycophenolate Mofetil
  • Natural Killer Cell Therapy
  • Rituximab
  • Tacrolimus
Treatment Plan 2 (NK cells, umbilical cord blood transplant)ExperimentalPatients receive high-dose lenalidomide PO QD on days -7 to -2, cyclophosphamide IV over 3 hours on day -7, and undergo TBI on day -3. Patients also receive rituximab and fludarabine phosphate as in Treatment Plan 1.
  • Cyclophosphamide
  • Fludarabine Phosphate
  • Lenalidomide
  • Mycophenolate Mofetil
  • Natural Killer Cell Therapy
  • Rituximab
  • Tacrolimus

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have one of the following hematologic malignancies: acute myelogenous
             leukemia (AML), induction failure, high-risk for relapse first remission (with
             intermediate-risk or high-risk cytogenetics, fms-related tyrosine kinase 3 [FLT3]
             mutation positive and/or evidence of minimal residual disease by flow cytometry),
             secondary leukemia from prior chemotherapy and/or arising from myelodysplastic
             syndrome, any disease beyond first remission

          -  Myelodysplastic syndrome (MDS): primary or therapy related

          -  Acute lymphoblastic leukemia (ALL): induction failure, primary refractory to treatment
             (do not achieve complete remission after first course of therapy) or are beyond first
             remission including second or greater remission or active disease; patients in first
             remission are eligible if they are considered high risk, defined as any of the
             following detected at any time: with t(9;22) or t(4;11), hypodiploidy, complex
             karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or
             evidence of minimal residual disease, or acute biphenotypic leukemia, or double hit
             non-Hodgkin's lymphoma

          -  Non-Hodgkin's lymphoma (NHL) in second or third complete remission, refractory NHL, or
             relapsed NHL (including relapse post autologous hematopoietic stem cell transplant);
             double hit lymphomas in first remission or more advanced disease

          -  Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with
             progressive disease following standard therapy; patients with progressive CLL
             following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus
             guidelines of indications for allogeneic stem cell transplantation; this includes
             patients with (1) lack of response or early relapse within 1 year of receiving a
             purine analog-containing treatment regimen, (2) disease relapse within 2 years of
             receiving a purine analog combination therapy or after other therapies such as
             autologous stem cell transplantation, and (3) CLL associated with tumor protein (p)53
             mutations or deletions and/or deletion (del) (17p) requiring therapy; patients must
             have chemosensitive disease with at least a partial response (PR) or stable disease
             (SD) with last treatment regimen

          -  Chronic myeloid leukemia (CML) second chronic phase or accelerated phase

          -  Hodgkin's disease (HD): induction failures, second or third complete remission, or
             relapse (including relapse post autologous hematopoietic stem cell transplant)

          -  Multiple myeloma: stage II or III, symptomatic, secretory multiple myeloma requiring
             treatment

          -  Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology
             Group (ECOG)

          -  Left ventricular ejection fraction greater than 45%

          -  Pulmonary function test (PFT) demonstrating a diffusion capacity of least 45%
             predicted

          -  Creatinine < 1.6 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal

          -  Bilirubin =< to 2.0 x normal

          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation
             and Mitigation Strategy (REMS) program, and be willing and able to comply with the
             requirements of the Revlimid REMS program

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS program

          -  Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing
             potential defined as not post-menopausal for 24 months or no previous surgical
             sterilization and willing to ongoing pregnancy testing while on treatment with
             lenalidomide

          -  Woman with child bearing potential must either commit to continued abstinence from
             heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
             effective method and one additional effective method AT THE SAME TIME, at least 4
             weeks before she starts taking lenalidomide

          -  Men must agree to use a latex condom during sexual contact with females of child
             bearing potential even if they have had a successful vasectomy

          -  Patients must have two CB units available which are matched with the patient at 4, 5,
             or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular)
             antigens; each cord must contain at least 1.5 x 10^7 total nucleated cells/Kg
             recipient body weight (pre-thaw); cord blood units will be procured through the
             National Marrow Donor Program (NMDP)

          -  Have identified a backup cells source in case of engraftment failure; the source can
             be autologous, related or unrelated

          -  Patients who have had a prior autologous transplant are eligible

        Exclusion Criteria:

          -  Patients with known history of human immunodeficiency virus (HIV)/acquired immune
             deficiency syndrome (AIDS)

          -  Active central nervous system (CNS) disease in patient with history of CNS malignancy

          -  Patients with chronic active hepatitis or cirrhosis; if positive hepatitis serology,
             the study chair may deem the patient eligible based on the results of liver biopsy

          -  Patients with known hypersensitivity to lenalidomide and/or rituximab

          -  Patients who have a matched related donor who is eligible and willing to donate stem
             cells
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Generation of a minimum of 5 x 10^6 natural killer/kg cells in at least 60% of patients (success rate)
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated with 90% credible interval.

Secondary Outcome Measures

Measure:Proportion of patients with acute graft-versus-host-disease
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Proportion of patients with chronic graft-versus-host-disease
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Overall survival
Time Frame:1 year
Safety Issue:
Description:The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Measure:Disease-free survival
Time Frame:1 year
Safety Issue:
Description:The product-limit estimator of Kaplan and Meier will be used with 95% confidence intervals.
Measure:Time to initial platelet recovery
Time Frame:From the infusion of peripheral blood stem cells to the first of 3 consecutive platelet count measurements tested on different days with a count greater than or equal to 20 x 10e9/L, assessed up to 1 year
Safety Issue:
Description:Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.
Measure:Time to initial absolute neutrophil count recovery
Time Frame:From the infusion of peripheral blood stem cells to the first of 3 consecutive days of an absolute neutrophil count greater than or equal to 0.5 x 10e9/L, assessed up to 1 year
Safety Issue:
Description:Cumulative incidence of platelet recovery will be estimated with the methods of Gooley, et al.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

February 11, 2020