Cord Blood Fucosylation to Enhance Homing and Engraftment in Patients With Hematologic Malignancies
4 other identifiers
interventional
33
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jul 2012
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2011
CompletedFirst Posted
Study publicly available on registry
November 11, 2011
CompletedStudy Start
First participant enrolled
July 13, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 25, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 25, 2017
CompletedApril 28, 2017
April 1, 2017
4.8 years
November 9, 2011
April 27, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants with engraftment within 42 days
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.
42 days
Mean Time to Engraftment
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.
Baseline to engraftment, assessed minimally 28 days post transplant
Study Arms (2)
Fludarabine/Clofarabine/Busulfan/Rituximab/TBI
EXPERIMENTALMyeloablative Regimen: Rituxan 375 mg/m\^2 (B cell malignancy) by vein (IV) on Day -10; Busulfan AUC 4,000 IV either as an outpatient prior to admission or as an inpatient on Day -9; 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.
Fludarabine + Melphalan
EXPERIMENTALReduced 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.
Interventions
140 mg/m2 by vein on Day -2 only for Fludarabine + Melphalan group.
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.
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).
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.
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.
375 mg/m\^2 by vein on Day -10 for B cell malignancy.
1.25 mg/Kg by vein on Day -4. 1.75 mg/Kg by vein on Day -3.
Busulfan per standard of care, test dose either as an outpatient prior to admission or as an inpatient on Day -9. Busulfan pharmacokinetics performed with test dose and the first dose on Day -7 per standard of care. Doses of Days -5 and -4 subsequently adjusted to target an AUC of 4,000 microMol.min-1.
30 mg/m\^2 IV Day -7 to Day -4;
2 Gy in AM of Day -3.
Eligibility Criteria
You may qualify if:
- 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,
- Myelodysplastic Syndrome (MDS): Primary or therapy related; or,
- 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,
- Non-Hodgkin's Lymphoma (NHL) in primary induction failure, second or third complete remission, refractory disease, or relapse (including relapse post autologous hematopoietic stem cell transplant). Double hit lymphomas in first remission or more advanced disease; or,
- Small Lymphocytic Lymphoma (SLL), or Chronic Lymphocytic Leukemia (CLL) with progressive disease following standard therapy; or,
- CML second chronic phase or accelerated phase; or,
- Hodgkin's Disease (HD): Induction failures, second or third complete remission, or relapse (including relapse post autologous hematopoietic stem cell transplant).
- Patients Age Criteria: Age \>/= 1 and \</= 80 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
- 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).
- 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.
- 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.
- 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).
- Have identified a back-up cell source in case of engraftment failure. The source can be autologous, related or unrelated.
You may not qualify if:
- Patients with known history of HIV/AIDS.
- Active 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- American Stem Cell, Inc.collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Popat U, Mehta RS, Rezvani K, Fox P, Kondo K, Marin D, McNiece I, Oran B, Hosing C, Olson A, Parmar S, Shah N, Andreeff M, Kebriaei P, Kaur I, Yvon E, de Lima M, Cooper LJ, Tewari P, Champlin RE, Nieto Y, Andersson BS, Alousi A, Jones RB, Qazilbash MH, Bashir Q, Ciurea S, Ahmed S, Anderlini P, Bosque D, Bollard C, Molldrem JJ, Chen J, Rondon G, Thomas M, Miller L, Wolpe S, Simmons P, Robinson S, Zweidler-McKay PA, Shpall EJ. Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation. Blood. 2015 May 7;125(19):2885-92. doi: 10.1182/blood-2015-01-607366. Epub 2015 Mar 16.
PMID: 25778529DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth Shpall, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2011
First Posted
November 11, 2011
Study Start
July 13, 2012
Primary Completion
April 25, 2017
Study Completion
April 25, 2017
Last Updated
April 28, 2017
Record last verified: 2017-04