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Cord Blood (CB) Ex-vivo Mesenchymal Stem Cell (MSC) Expansion + Fucosylation

This study is not yet open for participant recruitment.
Verified September 2017 by M.D. Anderson Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT03096782
First Posted: March 30, 2017
Last Update Posted: September 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Mesoblast, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
  Purpose

Umbilical cord blood is a source of blood-forming cells that can be used for a transplant. The cord blood cells being transplanted in this study will be from a donor. Before the cord blood is given to you, researchers will grow the cord blood cells in a laboratory.

Expanding cord blood means to change the blood in the laboratory. To expand the cord blood, researchers will grow the blood cells on a special layer of cells called mesenchymal precursor cells (MPCs) collected from the bone marrow of healthy volunteers and grown in a laboratory. This is designed to increase the number of expanded cells that can be collected. A type of sugar will also be added to the cell membrane of blood cells in the laboratory, which may help your blood counts to recover faster.

As part of standard care, patients normally receive 2 units of non-expanded cord blood.

The goal of this clinical research study is to learn if giving 1 unit of expanded cord blood with added sugar and 1 unit of non-expanded cord blood (no added sugar) to a patient with leukemia or lymphoma can help the transplant to "take" faster. The safety of this combination will also be studied. Chemotherapy and/or 1 dose of radiation therapy will also be given before the transplant.

This is an investigational study. Expanded cord blood cells with MPCs and adding sugar are not FDA-approved processes. Both processes are currently being used for research purposes only. Fludarabine, busulfan, clofarabine, melphalan, mycophenolate mofetil (MMF), tacrolimus, and rituximab are FDA approved and commercially available to be given to patients with leukemia or lymphoma having a cord blood transplant. Total body irradiation is delivered using FDA-approved and commercially available methods. The study doctor can explain how the study treatments are designed to work.

Up to 25 participants will be enrolled in this study. All will take part at MD Anderson.


Condition Intervention Phase
Hematopoietic/Lymphoid Cancer Drug: Busulfan Drug: Rituximab Drug: ATG Drug: Fludarabine Drug: Clofarabine Radiation: Total Body Irradiation Procedure: Cord Blood Transplant Drug: Mycofenolate mofetil Drug: Tacrolimus Drug: G-CSF Drug: Melphalan Drug: Cyclophosphamide Drug: Mesna Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Cord Blood Ex-vivo Mesenchymal Stem Cell (MSC) Expansion Plus Fucosylation to Enhance Homing and Engraftment

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 25
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Plan 1: Fludarabine/Clofarabine/Busulfan/Rituximab/TBI

If participant between 1 and 55 years of age and can receive high-dose chemotherapy, or if participant between 55 and 65 years old and participant's doctor agrees, participant receives fludarabine, clofarabine, busulfan, antithymocyte globulin (ATG), total body irradiation, and possibly rituximab.

Test dose of busulfan given as outpatient or inpatient.

Rituximab given by decision of physician on Day -11.

ATG given on Days -9 and -8.

Fludarabine, clofarabine, and busulfan given on Days -7 through -4.

Single treatment of low-dose total body irradiation n Day -3.

Cord blood transplant given on Day 0.

MMF starting on Day -3 twice a day.

Tacrolimus on Day -2 until able to take it by mouth. Then tacrolimus by mouth 2 times a day for about 6 months.

Filgrastim (G-CSF) 1 time a day every day starting on Day 0 until white blood count begins to recover.

Drug: Busulfan
Busulfan test dose administered either as an outpatient prior to admission or as an inpatient on Day -10. Busulfan pharmacokinetics performed with the test dose and the first dose on Day -7 per standard of care. The doses of Days -6, -5, and -4 subsequently adjusted to target an AUC of 4,000 microMol.min-1. In the event that PK adjusting not possible a dose of Busulfan of 130 mg/m2 administered.
Other Names:
  • Busulfex
  • Myleran
Drug: Rituximab
Rituximab 375 mg/m given by vein for B cell malignancy on Day -11.
Other Name: Rituxan
Drug: ATG

Plan 1: Rabbit ATG 1.25 mg/Kg by vein on Day -9, and 1.75 mg/Kg on Day -8.

Plan 2 and Plan 3: Rabbit ATG 1.25 mg/Kg by vein on Day -8, and 1.75 mg/Kg on Day -7.

Other Names:
  • ATG(rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • Rabbit ATG
  • rATG
  • Thymoglobulin
Drug: Fludarabine

Plan 1: 10 mg/m2 by vein on Days -7 to -4.

Plan 2: 40 mg/m2 by vein on Days -5 to -2.

Plan 3: 40 mg/m2 by vein on Days -6 to -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Clofarabine
30 mg/m2 by vein on Days -7 to -4.
Other Names:
  • Clofarex
  • Clolar
Radiation: Total Body Irradiation

Plan 1: Low-Dose TBI 2 Gy given on Day -3.

Plan 3: 200 cGy given on Day -1.

Other Names:
  • TBI
  • XRT
  • External Beam Radiotherapy
Procedure: Cord Blood Transplant
Cord Blood Transplant on Day 0.
Other Name: Cord blood infusion
Drug: Mycofenolate mofetil
15mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Days -3 to Day +100 in the absence of graft versus host disease.
Other Names:
  • MMF
  • CellCept
Drug: Tacrolimus
Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no graft versus host disease present.
Other Name: Prograf
Drug: G-CSF
350 mg subcutaneously daily starting on Day 0 until engraftment.
Other Names:
  • Filgrastim
  • Neupogen
Experimental: Plan 2: Fludarabine/Melphalan

If participant's doctor chooses fludarabine and melphalan:

On Day -9, participant admitted to the hospital and receives fluids by vein.

On Days -8 and -7, participant receives ATG by vein over about 4 hours.

On Days -5, -4, and -3, participant receives fludarabine by vein over about 30 minutes.

On Day -2, participant receives fludarabine by vein over about 30 minutes and melphalan by vein over about 30 minutes.

On Day 0, participant receives cord blood transplant through the CVC.

MMF starting on Day -3 twice a day.

Tacrolimus on Day -2 until able to take it by mouth. Then tacrolimus by mouth 2 times a day for about 6 months.

Filgrastim (G-CSF) 1 time a day every day starting on Day 0 until white blood count begins to recover.

Drug: ATG

Plan 1: Rabbit ATG 1.25 mg/Kg by vein on Day -9, and 1.75 mg/Kg on Day -8.

Plan 2 and Plan 3: Rabbit ATG 1.25 mg/Kg by vein on Day -8, and 1.75 mg/Kg on Day -7.

Other Names:
  • ATG(rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • Rabbit ATG
  • rATG
  • Thymoglobulin
Drug: Fludarabine

Plan 1: 10 mg/m2 by vein on Days -7 to -4.

Plan 2: 40 mg/m2 by vein on Days -5 to -2.

Plan 3: 40 mg/m2 by vein on Days -6 to -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Procedure: Cord Blood Transplant
Cord Blood Transplant on Day 0.
Other Name: Cord blood infusion
Drug: Mycofenolate mofetil
15mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Days -3 to Day +100 in the absence of graft versus host disease.
Other Names:
  • MMF
  • CellCept
Drug: Tacrolimus
Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no graft versus host disease present.
Other Name: Prograf
Drug: G-CSF
350 mg subcutaneously daily starting on Day 0 until engraftment.
Other Names:
  • Filgrastim
  • Neupogen
Drug: Melphalan
Plan 2: 140 mg/m by vein on Day -2.
Other Name: Alkeran
Experimental: Plan 3: Fludarabine/Cyclophosphamide/Total Body Irradiation

If participant's doctor chooses fludarabine, cyclophosphamide, and total body irradiation:

On Days -8 and -7, participant receives ATG by vein over about 4 hours.

On Day -6, participant receives fludarabine and cyclophosphamide. Mesna given before and after the cyclophosphamide dose.

On Days -5, -4, and -3, participant receives fludarabine.

On Day -1, participant receives a single treatment of low-dose total body irradiation.

On Day 0, participant receives cord blood transplant through the CVC.

MMF starting on Day -3 twice a day.

Tacrolimus on Day -2 until able to take it by mouth. Then tacrolimus by mouth 2 times a day for about 6 months.

Filgrastim (G-CSF) 1 time a day every day starting on Day 0 until white blood count begins to recover.

Drug: ATG

Plan 1: Rabbit ATG 1.25 mg/Kg by vein on Day -9, and 1.75 mg/Kg on Day -8.

Plan 2 and Plan 3: Rabbit ATG 1.25 mg/Kg by vein on Day -8, and 1.75 mg/Kg on Day -7.

Other Names:
  • ATG(rabbit)
  • Rabbit Antithymocyte Globulin
  • Rabbit Antilymphocyte Globulin
  • Rabbit ATG
  • rATG
  • Thymoglobulin
Drug: Fludarabine

Plan 1: 10 mg/m2 by vein on Days -7 to -4.

Plan 2: 40 mg/m2 by vein on Days -5 to -2.

Plan 3: 40 mg/m2 by vein on Days -6 to -3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Radiation: Total Body Irradiation

Plan 1: Low-Dose TBI 2 Gy given on Day -3.

Plan 3: 200 cGy given on Day -1.

Other Names:
  • TBI
  • XRT
  • External Beam Radiotherapy
Procedure: Cord Blood Transplant
Cord Blood Transplant on Day 0.
Other Name: Cord blood infusion
Drug: Mycofenolate mofetil
15mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or mouth from Days -3 to Day +100 in the absence of graft versus host disease.
Other Names:
  • MMF
  • CellCept
Drug: Tacrolimus
Starting dose 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no graft versus host disease present.
Other Name: Prograf
Drug: G-CSF
350 mg subcutaneously daily starting on Day 0 until engraftment.
Other Names:
  • Filgrastim
  • Neupogen
Drug: Cyclophosphamide
50 mg/kg by vein on Day -6.
Other Names:
  • Cytoxan
  • Neosar
Drug: Mesna
50 mg/kg by vein on Day -6.
Other Name: Mesnex

  Show Detailed Description

  Eligibility

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.


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

Inclusion Criteria:

  1. 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 MDS, Langerhan's cell histiocytosis, any disease beyond first remission.
  2. (#1, continued) b. Myelodysplastic Syndrome (MDS): MDS 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).
  3. (#1, continued) 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.
  4. (#1, continued) d. 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.
  5. (#1, continued) e. 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.
  6. (#1, continued) f. CML second chronic phase or accelerated phase.
  7. (#1, continued) g. 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.
  8. 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 MDACC pediatrician.
  9. Performance score of at least 80% by Karnofsky or PS < 3 (ECOG) (age >/= 12 years), or Lansky Play-Performance Scale of at least 60% or greater (age < 12 years).
  10. Adequate major organ system function as demonstrated by: a. Left ventricular ejection fraction of > 40%; b. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted. c. Creatinine </= 1.5 mg/dL for patients 12 years old and older and </= 1 for patients younger than 12 years old; d. SGPT/bilirubin </= to 2.0 x normal.
  11. Negative Beta 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.
  12. Patients must have two 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).
  13. Have identified a back up cells source in case of engraftment failure. The source can be autologous, related or unrelated.
  14. Patient must not have a 10/10 HLA matched family member or unrelated donor.
  15. Patients will have a back-up graft from any of the following: an available fraction of autologous marrow; or PBPCs harvested and cryopreserved; or family member donor; or a third cord blood unit.
  16. 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 TKI inhibitors as well as intra-thecal therapy are accepted exceptions).

Exclusion Criteria:

  1. Patients with known history of HIV/AIDS.
  2. Patients with positive hepatitis serology that is definitive of active disease.
  3. Active CNS disease in patient with history of CNS malignancy.
  4. 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.
  5. 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.
  6. 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.
  7. 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 Ph+ ALL is clinically refractory to available therapies with evidence of persistence in the bone marrow or peripheral blood.
  8. Patients with options for treatment that are known to be curative are not eligible.
  Contacts and Locations
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


Contacts
Contact: Amanda L. Olson, MD 713-792-8750 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Mesoblast, Inc.
Investigators
Principal Investigator: Amanda L. Olson, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03096782     History of Changes
Other Study ID Numbers: 2016-0051
First Submitted: March 21, 2017
First Posted: March 30, 2017
Last Update Posted: September 29, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
MDS
Acute Lymphoblastic Leukemia
ALL
Non-Hodgkin's Lymphoma
NHL
Small Lymphocytic Lymphoma
SLL
Chronic Lymphocytic Leukemia
CLL
Hodgkin's Disease
HD
Busulfan
Busulfex
Myleran
Rituximab
Rituxan
ATG
ATG(rabbit)
Rabbit Antithymocyte Globulin
Rabbit Antilymphocyte Globulin
Rabbit ATG
rATg
Thymoglobulin
Fludarabine
Fludarabine Phosphate
Fludara
Clofarabine

Additional relevant MeSH terms:
Cyclophosphamide
Tacrolimus
Fludarabine phosphate
Mycophenolate mofetil
Melphalan
Busulfan
Antilymphocyte Serum
Rituximab
Fludarabine
Clofarabine
Mycophenolic Acid
Lenograstim
Vidarabine
Mesna
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Calcineurin Inhibitors
Enzyme Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic