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Umbilical Cord Blood Transplant With Added Sugar and Chemotherapy and Radiation Therapy in Treating Patients With Leukemia or Lymphoma

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ClinicalTrials.gov Identifier: NCT03096782
Recruitment Status : Active, not recruiting
First Posted : March 30, 2017
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE March 21, 2017
First Posted Date  ICMJE March 30, 2017
Last Update Posted Date May 22, 2019
Actual Study Start Date  ICMJE October 13, 2017
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Feasibility of cord blood infusion [ Time Frame: At 12 months after transplant ]
    Will be defined by sterile expanded mesenchymal stem cell (MSC) product. Feasibility is defined as having a sterile expanded MSC product which was > 50% fucosylated in the majority of the patients enrolled.
  • Time to engraftment [ Time Frame: Up to 12 months after transplant ]
    The distribution of time to engraftment will be estimated using Kaplan-Meier plots and the relationship to covariates evaluated by piecewise exponential Bayesian regression. Time to engraftment will be monitored by the Bayesian statistical method of Thall et al., assuming an accrual rate of 10 patients per year with a maximum sample size of 25 patients. A mean time to engraftment (TTE) of 7 days will be considered desirable and a mean TTE of 21 days will be considered undesirable.
Original Primary Outcome Measures  ICMJE
 (submitted: March 24, 2017)
  • Feasibility of Cord Blood Infusion Expanded in Mesenchymal Stem Cells (MSC) with Fucosylation [ Time Frame: 12 months after the transplant ]
    Feasibility defined as having a sterile expanded MSC product which was >50% fucosylated in the majority of the patients enrolled.
  • Time to engraftment [ Time Frame: 28 days post stem cell infusion ]
    Engraftment defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion. A mean time to engraftment (TTE) of 7 days considered desirable and a mean TTE of 21 days considered undesirable.
Change History Complete list of historical versions of study NCT03096782 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2019)
  • Disease-free survival [ Time Frame: Up to12 months ]
    The distribution of disease-free survival time will be estimated using Kaplan-Meier plots and their relationships to covariates evaluated by piecewise exponential Bayesian regression.
  • Overall survival [ Time Frame: Up to 12 months after transplant ]
    The distribution of disease-free survival time will be estimated using Kaplan-Meier plots and their relationships to covariates evaluated by piecewise exponential Bayesian regression.
  • Treatment-related mortality (TRM) [ Time Frame: Up to 12 months after transplant ]
    TRM will be evaluated by tabulation, Kaplan-Meier plots, and piecewise exponential Bayesian regression.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2017)
Disease-free survival [ Time Frame: 1 year ]
Disease free survival estimated using Kaplan-Meier plots and their relationships to covariates evaluated by piecewise exponential Bayesian regression.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Umbilical Cord Blood Transplant With Added Sugar and Chemotherapy and Radiation Therapy in Treating Patients With Leukemia or Lymphoma
Official Title  ICMJE Cord Blood Ex-Vivo MSC Expansion Plus Fucosylation to Enhance Homing and Engraftment
Brief Summary This phase II trial studies how well an umbilical cord blood transplant with added sugar works with chemotherapy and radiation therapy in treating patients with leukemia or lymphoma. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem 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. The umbilical cord blood cells will be grown ("expanded") on a special layer of cells collected from the bone marrow of healthy volunteers in a laboratory. A type of sugar will also be added to the cells in the laboratory that may help the transplant to "take" faster.
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of transplantation of cord blood which is expanded in mesenchymal precursor cell (MPC) co-cultures then fucosylated with fucosyltransferase (FT)-VI and guanosine diphosphate (GDP) fucose prior to infusion in patients with hematologic malignancies following high-dose therapy.

II. To evaluate the time to engraftment using expanded fucosylated cord blood.

SECONDARY OBJECTIVES:

I. To evaluate the rate and severity of graft versus host disease. II. To evaluate the rates of infectious complications. III. To evaluate the rates of disease-free and overall survival.

OUTLINE: Patients are assigned to 1 of 3 groups.

GROUP I: Patients receive rituximab intravenously (IV) on day -11, anti-thymocyte globulin (ATG) IV over 4 hours on days -9 and -8, fludarabine IV over 1 hour, clofarabine IV over 1 hour, busulfan IV over 3 hours on days -7 through -4, and total body irradiation (TBI) on day -3. Patients then receive a cord blood transfusion IV on day 0.

GROUP II: Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -2. Patients then receive a cord blood transplant IV on day 0.

GROUP III: Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -3, cyclophosphamide IV over 1 hour on day -6, and one low-dose treatment of TBI on day -1. Patients then receive a cord blood transplant IV on day 0.

GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or orally (PO) twice daily (BID) on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz subcutaneously (SC) once daily (QD) starting on day 0 until white blood count begins to recover.

After completion of study treatment, patients are followed up at months 1, 3, 6, and 12.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Acute Biphenotypic Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Lymphoblastic Leukemia in Remission
  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  • Chemotherapy-Related Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Myelomonocytic Leukemia
  • Hodgkin Lymphoma
  • Langerhans Cell Histiocytosis
  • Minimal Residual Disease
  • Myelodysplastic Syndrome
  • Myelodysplastic Syndrome With Excess Blasts
  • Non-Hodgkin Lymphoma
  • Recurrent Hodgkin Lymphoma
  • Refractory Acute Lymphoblastic Leukemia
  • Refractory Myelodysplastic Syndrome
  • Small Lymphocytic Lymphoma
  • Therapy-Related Myelodysplastic Syndrome
Intervention  ICMJE
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
    • Antithymocyte Globulin
    • Antithymocyte Serum
    • ATG
    • ATGAM
    • ATS
    • Thymoglobulin
  • Drug: Busulfan
    Given IV
    Other Names:
    • 1, 4-Bis[methanesulfonoxy]butane
    • BUS
    • Bussulfam
    • Busulfanum
    • Busulfex
    • Busulphan
    • CB 2041
    • CB-2041
    • Glyzophrol
    • GT 41
    • GT-41
    • Joacamine
    • Methanesulfonic Acid Tetramethylene Ester
    • Methanesulfonic acid, tetramethylene ester
    • Mielucin
    • Misulban
    • Misulfan
    • Mitosan
    • Myeleukon
    • Myeloleukon
    • Myelosan
    • Mylecytan
    • Myleran
    • Sulfabutin
    • Tetramethylene Bis(methanesulfonate)
    • Tetramethylene bis[methanesulfonate]
    • WR-19508
  • Drug: Clofarabine
    Given IV
    Other Names:
    • Clofarex
    • Clolar
  • 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-sndz
    Given SC
    Other Names:
    • Filgrastim Biosimilar Filgrastim-sndz
    • Zarxio
  • Drug: Fludarabine
    Given IV
    Other Name: Fluradosa
  • 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
  • Drug: Mycophenolate Mofetil
    Given IV or PO
    Other Names:
    • Cellcept
    • MMF
  • 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
    Other Names:
    • FK 506
    • Fujimycin
    • Hecoria
    • Prograf
    • Protopic
  • Radiation: Total-Body Irradiation
    Undergo total body irradiation
    Other Names:
    • Total Body Irradiation
    • Whole-Body Irradiation
  • Procedure: Umbilical Cord Blood Transplantation
    Undergo cord blood transplant
    Other Names:
    • Cord Blood Transplantation
    • UCB transplantation
Study Arms  ICMJE
  • Experimental: Group I (chemotherapy, TBI, cord blood)

    Patients receive rituximab IV on day -11, ATG IV over 4 hours on days -9 and -8, fludarabine IV over 1 hour, clofarabine IV over 1 hour, busulfan IV over 3 hours on days -7 through -4, and TBI on day -3. Patients then receive a cord blood transfusion IV on day 0.

    GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover.

    Interventions:
    • Biological: Anti-Thymocyte Globulin
    • Drug: Busulfan
    • Drug: Clofarabine
    • Biological: Filgrastim-sndz
    • Drug: Fludarabine
    • Drug: Mycophenolate Mofetil
    • Biological: Rituximab
    • Drug: Tacrolimus
    • Radiation: Total-Body Irradiation
    • Procedure: Umbilical Cord Blood Transplantation
  • Experimental: Group II (chemotherapy, cord blood)

    Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -2. Patients then receive a cord blood transplant IV on day 0.

    GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover.

    Interventions:
    • Biological: Anti-Thymocyte Globulin
    • Biological: Filgrastim-sndz
    • Drug: Fludarabine
    • Drug: Melphalan
    • Drug: Mycophenolate Mofetil
    • Drug: Tacrolimus
    • Procedure: Umbilical Cord Blood Transplantation
  • Experimental: Group III (chemotherapy, TBI, cord blood)

    Patients receive ATG IV over 4 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -3, cyclophosphamide IV over 1 hour on day -6, and one low-dose treatment of TBI on day -1. Patients then receive a cord blood transplant IV on day 0.

    GVHD PROPHYLAXIS: All patients also receive mycofenolate mofetil IV over 2 hours or PO BID on days -3 with a taper beginning on day 100 in the absence of GVHD, tacrolimus IV or PO starting on day -2 for 6 months in the absence of GVHD, and filgrastim-sndz SC QD starting on day 0 until white blood count begins to recover.

    Interventions:
    • Biological: Anti-Thymocyte Globulin
    • Drug: Cyclophosphamide
    • Biological: Filgrastim-sndz
    • Drug: Fludarabine
    • Drug: Mycophenolate Mofetil
    • Drug: Tacrolimus
    • Radiation: Total-Body Irradiation
    • Procedure: Umbilical Cord Blood Transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 24, 2017)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2020
Estimated Primary Completion Date October 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have one of the following hematologic malignancies: a. Acute myelogenous leukemia (AML), induction failure, high-risk for relapse first remission (with intermediate-risk or high-risk cytogenetics, flt3 mutation positive and/or evidence of minimal residual disease by flow cytometry), secondary leukemia from prior chemotherapy and/or arising from myelodysplastic syndrome (MDS), Langerhan's cell histiocytosis, any disease beyond first remission. b. Myelodysplastic syndrome (MDS): MDS International Prognostic Scoring System (IPSS) INT-1 will be enrolled only if the subjects have failed previous leukemia treatments and are transfusion-dependent. MDS may be primary or therapy related, including patients that will be considered for transplant. Including the following categories: 1) Revised IPSS intermediate and high risk groups, 2) MDS with transfusion dependency, 3) Failure to respond or progression of disease on hypomethylating agents, 4) Refractory anemia with excess of blasts, 5) Transformation to acute leukemia, 6) Chronic myelomonocytic leukemia, 7) Atypical MDS/myeloproliferative syndromes, 8) Complex karyotype, abn(3g), -5/5g-, -7/7g-, abn(12p), abn(17p). c. Acute lymphoblastic leukemia (ALL) patients with the following will be considered: 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 translocations 9;22 or 4;11, hypodiploidy, complex karyotype, secondary leukemia developing after cytotoxic drug exposure, and/or evidence of minimal residual disease, or acute biphenotypic leukemia which excludes > 7 chromosomal abnormalities, or double hit non-Hodgkin's lymphoma. Non-Hodgkin's lymphoma (NHL) in second or third complete remission or relapse (including relapse post autologous hematopoietic stem cell transplant), or relapsed double hit lymphoma. Small lymphocytic lymphoma (SLL), or chronic lymphocytic leukemia (CLL) with progressive disease with progression after standard of care therapy or have failed/been intolerant to ibrutinib. Chronic myelogenous leukemia (CML) second chronic phase or accelerated phase. Hodgkin's disease (HD): Induction failure after the first complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant), or those with active disease.
  • The first 6 patients must be >= 18 and =< 65 years old. The subsequent patients may include pediatric patients >= 12 and =< 65 years old. Eligibility for pediatric patients will be determined in conjunction with an MD Anderson Cancer Center (MDACC) pediatrician.
  • Performance score of at least 80% by Karnofsky or performance score (PS) < 3 (Eastern Cooperative Oncology Group [ECOG]) (age >= 12 years)
  • Left ventricular ejection fraction of > 40%.
  • Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted.
  • Creatinine =< 1.5 mg/dL for patients 12 years old and older and =< 1 for patients younger than 12 years old.
  • Serum glutamate pyruvate transaminase (SGPT) =< to 2.0 x normal.
  • Bilirubin =< to 2.0 x normal.
  • Negative 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 and willing to use an effective contraceptive measure while on study.
  • Patients must have two cord blood (CB) units available which are matched with the patient at 4, 5, or 6/6 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).
  • Have identified a backup cells source in case of engraftment failure. The source can be autologous, related or unrelated.
  • Patient must not have a 10/10 HLA matched family member or unrelated donor.
  • Patients will have a back-up graft from any of the following: an available fraction of autologous marrow; or peripheral blood progenitor cells (PBPCs) harvested and cryopreserved; or family member donor; or a third cord blood unit.
  • Prior to initiating chemotherapy in this study, twenty-one or more days must have elapsed since the patient's last radiation or chemotherapy administration (Hydrea, Gleevec and other tyrosine kinase inhibitors [TKI] as well as intrathecal therapy are accepted exceptions).

Exclusion Criteria:

  • Patients with known history of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
  • Patients with positive hepatitis serology that is definitive of active disease.
  • 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 uncontrolled serious medical condition such as persistent septicemia despite adequate antibiotic therapy, decompensated congestive heart failure despite cardiac medications or pulmonary insufficiency requiring intubation (excluding primary disease for which CB transplantation is proposed), or psychiatric condition that would limit informed consent.
  • Positive beta HCG in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or breast-feeding.
  • Pediatric patients with acute lymphoblastic leukemia (ALL) that is t (9,22) positive in first remission are not eligible unless there is evidence of minimal residual disease after initial induction and/or consolidation treatment or the pediatric Philadelphia chromosome positive (Ph+) ALL is clinically refractory to available therapies with evidence of persistence in the bone marrow or peripheral blood.
  • Patients with options for treatment that are known to be curative are not eligible.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03096782
Other Study ID Numbers  ICMJE 2016-0051
NCI-2018-01236 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0051 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Amanda Olson M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP