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Trial record 41 of 52 for:    "Acute Leukemia" | "Anti-Bacterial Agents"

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

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.

Condition or disease Intervention/treatment Phase
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 Biological: Anti-Thymocyte Globulin Drug: Busulfan Drug: Clofarabine Drug: Cyclophosphamide Biological: Filgrastim-sndz Drug: Fludarabine Drug: Melphalan Drug: Mycophenolate Mofetil Biological: Rituximab Drug: Tacrolimus Radiation: Total-Body Irradiation Procedure: Umbilical Cord Blood Transplantation Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cord Blood Ex-Vivo MSC Expansion Plus Fucosylation to Enhance Homing and Engraftment
Actual Study Start Date : October 13, 2017
Estimated Primary Completion Date : October 31, 2020
Estimated Study Completion Date : October 31, 2020


Arm Intervention/treatment
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.

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

Biological: Filgrastim-sndz
Given SC
Other Names:
  • Filgrastim Biosimilar Filgrastim-sndz
  • Zarxio

Drug: Fludarabine
Given IV
Other Name: Fluradosa

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

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.

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

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

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

Procedure: Umbilical Cord Blood Transplantation
Undergo cord blood transplant
Other Names:
  • Cord Blood Transplantation
  • UCB 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.

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

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: Mycophenolate Mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF

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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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): NCT03096782


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Amanda Olson M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03096782     History of Changes
Other Study ID Numbers: 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 )
First Posted: March 30, 2017    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 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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Antibiotics, Antineoplastic
Antibiotics, Antitubercular
Anti-Bacterial Agents
Lymphoma
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Hodgkin Disease
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid, Accelerated Phase
Neoplasm, Residual
Leukemia, Biphenotypic, Acute
Histiocytosis, Langerhans-Cell
Myelodysplastic Syndromes
Histiocytosis
Anemia, Refractory, with Excess of Blasts
Syndrome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease