Cord Blood Fucosylation

This study is currently recruiting participants.
Verified February 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01471067
First received: November 9, 2011
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

The goal of this clinical research study is to learn if it is safe and feasible to transplant changed cord blood for patients with leukemia or lymphoma. Researchers also want to learn if this can help to control the disease.

The cord blood will be changed to make use of sugar that is found in small amounts in blood cells. It plays a role in signaling where in the body the transplanted cells should go to. Adding more sugars to the cord blood cells in the laboratory is designed to help the cord blood cells find their way faster to the bone marrow. This may help your blood counts to recover faster. This process is called fucosylation.

Anti-thymocyte globulin (ATG) is a protein that removes immune cells that cause damage to the body.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Fludarabine is designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die. This chemotherapy is also designed to block your body's ability to reject the donor's bone marrow cells.

Melphalan and busulfan are designed to bind to the DNA of cells, which may cause cancer cells to die.

Mycophenolate mofetil (MMF) and tacrolimus are designed to block the donor cells from growing and spreading in a way that could cause graft versus host disease (GVHD -- a condition in which transplanted tissue attacks the recipient's body). This may help to prevent GVHD.

Rituximab is designed to attach to cancer cells, which may cause them to die.


Condition Intervention Phase
Blood And Marrow Transplantation
Leukemia
Lymphoma
Transplantation Infection
Transplantation, Bone Marrow
Drug: Melphalan
Drug: Fludarabine
Drug: Mycophenolate mofetil
Drug: Tacrolimus
Procedure: Cord Blood Infusion
Drug: Rituximab
Drug: ATG
Drug: Busulfan
Drug: Clofarabine
Radiation: Total Body Irradiation (TBI)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Participants with engraftment within 42 days [ Time Frame: 42 days ] [ Designated as safety issue: No ]
    Engraftment is 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.

  • Mean Time to Engraftment [ Time Frame: Baseline to engraftment, assessed minimally 28 days post transplant ] [ Designated as safety issue: No ]
    Engraftment date is the first day of three (3) consecutive days that the absolute neutrophil count (ANC) exceeds 0.5 x109/L. Time measured in days.


Estimated Enrollment: 50
Study Start Date: July 2012
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine/Clofarabine/Busulfan/Rituximab/TBI
Myeloablative Regimen: Rituxan 375 mg/m^2 (B cell malignancy) by vein (IV) on Day -10; Busulfan AUC 5,000 IV Day -7 to Day -4; Clofarabine 30 mg/m^2 IV Day -7 to Day -4; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; Fludarabine 10 mg/m^2 IV on Days -7 to -4; Total Body Irradiation (TBI) 2 Gy on Day -3; with Cord Blood infusions on Day 0.
Drug: Fludarabine
10 mg/m2 by vein on Days -7 to -4 for Melphalan + Thiotepa + Fludarabine group, or 40 mg on Days -5 to -2 for Fludarabine + Melphalan group.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Mycophenolate mofetil
15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth twice a day from Days -3 to +100 in the absence of Graft vs Host Disease (GvHD).
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 vs Host Disease (GvHD) is present.
Other Name: Prograf
Procedure: Cord Blood Infusion
Cord blood infusion on Day 0. Each participant will receive cells from one unexpanded cord blood sample plus cells from a second cord blood sample that has undergone fucosylation.
Other Name: blood and bone marrow transplantation
Drug: Rituximab
375 mg/m^2 by vein on Day -10 for B cell malignancy.
Other Name: Rituxan
Drug: ATG

1.25 mg/Kg by vein on Day -4.

1.75 mg/Kg by vein on Day -3.

Other Names:
  • Antithymocyte Globulin
  • Thymoglobulin
Drug: Busulfan
Busulfan per standard of care, test dose either outpatient before Day -14 or inpatient on Day -9. Busulfan pharmacokinetics performed with test dose and the first dose on Day -7 per standard of care. Doses of Days -6 to -4 subsequently adjusted to target an AUC of 5,000 microMol.min-1
Other Names:
  • Bu
  • Myleran
  • Busulfex
Drug: Clofarabine
30 mg/m^2 IV Day -7 to Day -4;
Other Names:
  • Clofarex
  • Clolar
Radiation: Total Body Irradiation (TBI)
2 Gy in AM of Day -3.
Other Name: XRT
Experimental: Fludarabine + Melphalan
Reduced Intensity: Fludarabine 40 mg/m^2 IV on Days -5 to -2; Melphalan 140 mg/m^2 IV on Day -2; ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3; with Cord Blood infusions on Day 0.
Drug: Melphalan
140 mg/m2 by vein on Day -2 only for Fludarabine + Melphalan group.
Other Name: Alkeran
Drug: Fludarabine
10 mg/m2 by vein on Days -7 to -4 for Melphalan + Thiotepa + Fludarabine group, or 40 mg on Days -5 to -2 for Fludarabine + Melphalan group.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Mycophenolate mofetil
15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth twice a day from Days -3 to +100 in the absence of Graft vs Host Disease (GvHD).
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 vs Host Disease (GvHD) is present.
Other Name: Prograf
Procedure: Cord Blood Infusion
Cord blood infusion on Day 0. Each participant will receive cells from one unexpanded cord blood sample plus cells from a second cord blood sample that has undergone fucosylation.
Other Name: blood and bone marrow transplantation
Drug: ATG

1.25 mg/Kg by vein on Day -4.

1.75 mg/Kg by vein on Day -3.

Other Names:
  • Antithymocyte Globulin
  • Thymoglobulin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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, 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; or,
  2. Myelodysplastic Syndrome (MDS): Primary or therapy related; or,
  3. 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 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, or double hit non-Hodgkin's lymphoma; or,
  4. Non-Hodgkin's Lymphoma (NHL) in second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease; or,
  5. Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy; or,
  6. CML second chronic phase or accelerated phase; or,
  7. Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
  8. Patients Age Criteria: Age >/= 1 and </= 80 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 at least 40-45% b. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted. For children </= 7 years of age who are unable to perform PFT, oxygen saturation >/= 92% on room air by pulse oximetry. c. Creatinine < 1.6 mg/dL. 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 cell source in case of engraftment failure. The source can be autologous, related or unrelated.

Exclusion Criteria:

  1. Patients with known history of HIV/AIDS.
  2. Active CNS disease in patient with history of CNS malignancy.
  3. 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.
  4. 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.
  5. 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01471067

Contacts
Contact: Elizabeth Shpall, MD 713-745-2161

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Elizabeth Shpall, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01471067     History of Changes
Other Study ID Numbers: 2010-0658, NCI-2011-03742
Study First Received: November 9, 2011
Last Updated: February 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Blood And Marrow Transplantation
Cord blood transplant
Cord Blood Fucosylation
Leukemia
Lymphoma
Pediatrics
Hematologic Malignancies
Acute Myelogenous Leukemia
AML
Myelodysplastic Syndrome
MDS
High-risk cytogenetics
Secondary leukemia from prior chemotherapy
Langerhan's cell histiocytosis
Acute Lymphoblastic Leukemia
ALL
complete remission
Philadelphia chromosome
translocation 4;11
Hypodiploidy
Chronic Myeloid Leukemia
CML
Non-Hodgkin's Lymphoma
NHL
Hodgkin's Disease
HD
Chronic Lymphocytic Leukemia
CLL
Melphalan
Alkeran

Additional relevant MeSH terms:
Leukemia
Lymphoma
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Hematologic Diseases
Antilymphocyte Serum
Busulfan
Melphalan
Mycophenolate mofetil
Fludarabine monophosphate
Tacrolimus
Rituximab
Fludarabine
Clofarabine
Mycophenolic Acid
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014