Cord Blood Expansion on Mesenchymal Stem Cells

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborators:
ViaCell
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00498316
First received: July 6, 2007
Last updated: August 22, 2014
Last verified: August 2014
  Purpose

The goal of this clinical research study is to learn if combining cord blood units will be safe and result in the cells "taking" faster in recipients. The cord blood units will have their cell number increased in the lab using cells from a family member or they will be collected from an unrelated healthy donor.


Condition Intervention Phase
Myelodysplastic Syndrome
Leukemia
Procedure: Cord Blood Infusion
Drug: Busulfan
Drug: Fludarabine
Drug: Rituximab
Other: ATG
Drug: Cyclophosphamide
Drug: Clofarabine
Radiation: Total Body Irradiation (TBI)
Drug: Melphalan
Drug: Tacrolimus
Drug: Mycophenolate Mofetil
Drug: G-CSF
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cord Blood Expansion on Mesenchymal Stem Cells

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Engraftment and Time to Engraftment [ Time Frame: 100 days after transplant, then every 3 months thereafter ] [ Designated as safety issue: Yes ]
    Engraftment defined as a sustained ANC > 0.5 x 109/L for 3 consecutive days and evidence of donor chimerism or autologous reconstitution by D+42


Estimated Enrollment: 125
Study Start Date: July 2007
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Cord Blood Infusion

Cord blood transplantation performed on day 0. Busulfan 32 mg/m2 by vein as an outpatient before Day -14 or as an inpatient on Day -9, and AUC of 4,000 microMol.min-1 by vein on Days -7 to -4.

Fludarabine 10 mg/m2 by vein on Days -7 to -4, 40 mg/m2 by vein on Days -6 to -3 or on Days -5 to -2.

Rituximab 375 mg/m2 by vein on Day -9. ATG 1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3, 1.25 mg/kg by vein on Day -3 and 1.75 mg/kg by vein on Day -2.

Cyclophosphamide 50 mg/kg by vein on Day -6. Clofarabine 30 mg/m2 by vein on Days -7 to -4. Total body irradiation (TBI) 200 cGy at 25 cGy/minute delivered on Day -3. Melphalan 140 mg/m2 by vein on Day -2. Tacrolimus 0.03 mg/kg by vein daily starting on D-2, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered around Day +180, if no GVHD is present.

Procedure: Cord Blood Infusion
Cord blood transplantation performed on day 0.
Drug: Busulfan
32 mg/m2 by vein as an outpatient before Day -14 or as an inpatient on Day -9, and AUC of 4,000 microMol.min-1 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are >1 and < 55 years old. Patients >55 but < 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine

10 mg/m2 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are >1 and < 55 years old. Patients >55 but < 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).

40 mg/m2 by vein on Days -6 to -3 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are > 55 and < 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.

40 mg/m2 by vein on Days -5 to -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are >1 and < 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.

Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Rituximab
375 mg/m2 by vein on Day -9 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are > 55 and < 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.
Other Name: Rituxan
Other: ATG

1.25 mg/Kg by vein on Day -4 and 1.75 mg/Kg by vein on Day -3 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are > 55 and < 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.

1.25 mg/kg by vein on Day -3 and 1.75 mg/kg by vein on Day -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are >1 and < 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.

Other Names:
  • Antithymocyte Globulin
  • Thymoblobulin
Drug: Cyclophosphamide
50 mg/kg by vein on Day -6 for patients with AML, ALL, NHL, CLL,CML, HD and MM who are > 55 and < 80 years old or of any age with co-morbid condition that in the opinion of the investigators would preclude myeloablative therapy.
Other Names:
  • Cytoxan
  • Neosar
Drug: Clofarabine
30 mg/m2 by vein on Days -7 to -4 for patients with ALL, AML, NHL, CLL, CML, HD, and MM who are >1 and < 55 years old. Patients >55 but < 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).
Other Names:
  • Clofarex
  • Clolar
Radiation: Total Body Irradiation (TBI)
200 cGy at 25 cGy/minute delivered on Day -3.
Other Names:
  • TBI
  • XRT
Drug: Melphalan
140 mg/m2 by vein on Day -2 for patients with AML, ALL, NHL, CLL, CML, and HD who are >1 and < 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive the reduced intensity treatment regimen 3.
Other Name: Alkeran
Drug: Tacrolimus
0.03 mg/kg by vein daily starting on D-2, to be changed to oral dosing when tolerated. Tacrolimus is to be tapered around Day +180, if no GVHD is present.
Other Name: Prograf
Drug: Mycophenolate Mofetil
1 gram by vein twice a day Days -3 through Day 100.
Other Names:
  • MMF
  • CellCept
Drug: G-CSF
5 mcg/kg/day subcutaneously beginning on day 0, and continuing until the absolute neutrophil count (ANC) is > 2.5 x 109/L.
Other Names:
  • Filgrastim
  • Neupogen

  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.
  4. #3, continued: 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,
  5. 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,
  6. Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy; or,
  7. CML second chronic phase or accelerated phase; or,
  8. Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant); or,
  9. Multiple Myeloma: stage II or III, symptomatic, secretory Multiple Myeloma requiring treatment.
  10. Age greater than or equal to 1 year but less than or equal to 55 years (Myeloablative Regimen 4). Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician. Patients >55 but < 65 years who have a Performance Status of 0 or 1 and no comorbidities may receive the myeloablative regimen 4 at the discretion of the investigator(s).
  11. Age greater than 55 years and less than or equal to 80 years (Nonmyeloablative Regimen 2)
  12. Age greater than or equal to 1 but less than or equal to 80 years old that in the opinion of the investigator(s) would preclude myeloablative therapy and who cannot receive Total Body Irradiation (TBI) may receive reduced intensity regimen 3.
  13. Performance score of at least 60% by Karnofsky or PS less than 3 (ECOG) (age greater than or equal to 12 years), or Lansky Play-Performance Scale of at least 60% or greater (age <12 years)
  14. Left ventricular ejection fraction of at least 40% (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or 30% (Nonmyeloablative Regimen 2)
  15. Pulmonary function test demonstrating a diffusion capacity of least 50% predicted (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or at least 40% predicted (Nonmyeloablative Regimen 2). For children < 7 years of age who are unable to perform PFT, oxygen saturation > 92% on room air by pulse oximetry.
  16. Creatinine < 1.6 mg/dL (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or < 3.0 mg/dL (Nonmyeloablative Regimen 2).
  17. SGPT/bilirubin < / = to 2.0 x normal (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or < / = 4.0 x normal (Nonmyeloablative Regimen 2)
  18. 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.
  19. Unrelated Cord Blood will be used as a source of hematopoietic support if a 5 or 6/6 related or 6/6 unrelated bone marrow donor is not available, or if the tempo of a patient's disease dictates it is not in the patient's best interest to wait for an unrelated marrow donor to be procured.
  20. Patients must have two Cord Blood 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 10 million total nucleated cells/Kg recipient body weight (pre-thaw)
  21. Patients must have a family member who is matched at 2, 3, or 4 HLA antigens typed as described above and willing to donate 80-100 ml or bone marrow for MSC generation or the Angioblast Mesenchymal Precursor Cells will be used for the cord blood co-cultures. Patients that are high risk for relapse are eligible to use the Angioblast "off-the-shelf" Mesenchymal Precursor Cells.
  22. Have identified a back-up cell source in case of engraftment failure. The source can be autologous, related, or unrelated.

Exclusion Criteria:

  1. HIV positive
  2. 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.
  3. 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.
  4. Active CNS disease in patient with history of CNS malignancy.
  5. Availability of appropriate, willing, HLA-matched related marrow donor.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00498316

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

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

Additional Information:
No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00498316     History of Changes
Other Study ID Numbers: 2005-0781, NCI-2011-02823, RP100469 02, 1P01CA148600-01A1, 5R01CA061508-20
Study First Received: July 6, 2007
Last Updated: August 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Myelodysplastic Syndrome
Leukemia
Cord Blood Expansion
Umbilical Cord Blood
Mesenchymal Stem Cells
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
ALL
AML
MDS

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Melphalan
Mycophenolate mofetil
Fludarabine phosphate
Tacrolimus
Rituximab
Fludarabine
Clofarabine
Mycophenolic Acid
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 28, 2014