Cord Blood Expansion on Mesenchymal Stem Cells - Full Text View

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 ]

Estimated Enrollment:	125
Study Start Date:	July 2007
Estimated Primary Completion Date:	July 2014 (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 5,000 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 -1. 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 5,000 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 -1 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

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 5,000 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 -1. 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 5,000 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 -1

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:

Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS): 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, second or third complete remission, or second relapse.
Acute Lymphoblastic Leukemia (ALL): induction failure, first complete remission with Philadelphia chromosome or translocation (4;11), hypodiploidy, and/or evidence of minimal residual disease by flow cytometry;second third complete remission, or second relapse.
CML second chronic phase or accelerated phase.
Non-Hodgkin's Lymphoma (NHL): Induction failures, second or third complete remission, or relapse (including relapse post autologous)
Hodgkin's Disease (HD): Induction failures, second or third complete remission,or relapse (including relapse post autologous hematopoietic stem cell transplant).
Chronic Lymphocytic Leukemia (CLL): Progressive disease following standard therapy
Multiple Myeloma: stage II or III , symptomatic , secretory Multiple Myeloma requiring treatment.
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).
Age greater than 55 years and less than or equal to 80 years (Nonmyeloablative Regimen 2)
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.
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)
Left ventricular ejection fraction of at least 40% (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or 30% (Nonmyeloablative Regimen 2)
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.
Creatinine < 1.6 mg/dL (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or < 3.0 mg/dL (Nonmyeloablative Regimen 2).
SGPT/bilirubin < / = to 2.0 x normal (Myeloablative Regimen 4, Reduced Intensity Regimen 3) or < / = 4.0 x normal (Nonmyeloablative Regimen 2)
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.
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.
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)
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.
Patient must be willing to undergo bone marrow harvest or peripheral blood progenitor cells collection for use in case of engraftment failure.
If the patient is unable / fails to successfully undergo autologous bone marrow harvest or peripheral blood progenitor cells collection a family member must be identified who agrees to donate bone marrow or peripheral blood progenitor cells for T-depleted transplant. A third cord blood unit could be used in case of engraftment failure. This cord blood unit must be identified prior to enrollment in this study.
If the family member is to be used as the donor, he/she must freely document his / her willingness to comply with this donation by signing a donor informed consent form prior to preparative regimen for transplantation. This donor could be the same person who donates the bone marrow aspirate for mesenchymal stem cell generation

Exclusion Criteria:

HIV positive
Positive Pregnancy Test
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.
Patients with active (untreated) CNS disease
Availability of appropriate, willing, HLA-matched related marrow donor.

Contacts and Locations

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

Contacts

Contact: Elizebeth Shpall, MD

713-745-2161

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Elizabeth Shpall, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Elizabeth Shpall, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided by M.D. Anderson Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

de Lima M, McNiece I, Robinson SN, Munsell M, Eapen M, Horowitz M, Alousi A, Saliba R, McMannis JD, Kaur I, Kebriaei P, Parmar S, Popat U, Hosing C, Champlin R, Bollard C, Molldrem JJ, Jones RB, Nieto Y, Andersson BS, Shah N, Oran B, Cooper LJ, Worth L, Qazilbash MH, Korbling M, Rondon G, Ciurea S, Bosque D, Maewal I, Simmons PJ, Shpall EJ. Cord-blood engraftment with ex vivo mesenchymal-cell coculture. N Engl J Med. 2012 Dec 13;367(24):2305-15. doi: 10.1056/NEJMoa1207285.

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00498316 History of Changes
Other Study ID Numbers:	2005-0781
Study First Received:	July 6, 2007
Last Updated:	February 22, 2013
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 monophosphate
Tacrolimus

Rituximab
Fludarabine
Clofarabine
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 19, 2013