Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen

This study is currently recruiting participants.
Verified March 2014 by St. Jude Children's Research Hospital
Sponsor:
Collaborators:
The Hartwell Foundation
Assisi Foundation
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT01328496
First received: March 31, 2011
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched related/sibling donor (MSD), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive an umbilical cord blood transplantation (UCBT) using a myeloablative preparative regimen.

The preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2. Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.


Condition Intervention Phase
Hematologic Malignancies
Disorder Related to Transplantation
Hematopoietic Malignancy
Genetic: Preparative Regimen
Phase 2

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: Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Event Free survival at one- year post transplant will be estimated for research participants by using single unit umbilical cord blood [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Specifically, event free survival is calculated as the difference between date of HCT and min (last follow-up date, date of relapse, date of graft failure, date of death due to any cause, 1 year post-transplant).


Secondary Outcome Measures:
  • The clinical outcome of patients undergoing a double unit UCBT will be described by engraftment, relapse/death status [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    For patients enrolled in the observation arm their clinical outcomes such as engraftment, acute and chronic GVHD, relapse/death status, and transplant related mortality/morbidity will be described.

  • The incidence and severity of acute and chronic GVHD of patients enrolled in the research arm will be estimated . [ Time Frame: 1 years ] [ Designated as safety issue: No ]
    The cumulative incidence of acute and chronic GVHD will be estimated using Gray's method and death is the competing risk event.

  • Time to neutrophil and platelet engraftment as well as the incidence of engraftment among patients enrolled in the research arm will be estimated. method [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    A descriptive statistics for time to engraftment for patients that achieve neutrophil and platelet engraftment will be provided. The cumulative incidence of engraftment will be estimated .

  • The incidence of TRM and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research arm will be estimated . [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The cumulative incidence of TRM and transplant related morbidity will be estimated .TRM is death occurring in patients in continuous complete remission.


Estimated Enrollment: 43
Study Start Date: June 2011
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Research Arm

Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.

Intervention: Preparative Regimen

Genetic: Preparative Regimen

Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.

Observation Arm

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.

Intervention: Preparative Regimen

Genetic: Preparative Regimen

Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.

Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.


Detailed Description:

The primary objectives is to estimate the event-free survival (EFS) at one-year post-transplant for research participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT) using single unit umbilical cord blood (UCB).

Secondary objectives are:

  • Describe the clinical outcome of patients undergoing a double unit UCBT.
  • Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) of patients enrolled in the research arm.
  • Estimate the incidence and time to neutrophil and platelet engraftment among patients enrolled in the research arm.
  • Estimate the incidence of transplant related mortality (TRM) and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research

Exploratory Objectives are:

  • Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
  • Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) and spectratyping. Immunophenotyping and functional assays of T, B and NK cells and lymphocytes will also be evaluated.
  • Evaluate the determinants of engraftment.
  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age less than or equal to 21 years old.
  • Has a partially HLA-matched single or double UCB product
  • High-risk hematologic malignancy.
  • High risk ALL in CR1, ALL in High risk CR2, ALL in CR3 or subsequent.
  • AML in high risk CR1, AML in CR2 or subsequent
  • AML in first relapse with < 25% blasts in BM
  • Therapy related AML, with prior malignancy in CR > 12mo
  • MDS, primary or secondary
  • NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
  • CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
  • Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT.
  • Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT.
  • JMML
  • All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.

Patient must fulfill pre-transplant evaluation:

  • Cardiac shortening fraction ≥ 26%.
  • Creatinine clearance ≥ 70 ml/min/1.73m2.
  • Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry ≥ 92% on room air.
  • Karnofsky (≥ 16 years) or Lansky (<16 years) performance score ≥ 70
  • Bilirubin ≤ 2.5 mg/dL.
  • Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.
  • Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.

Exclusion Criteria:

  • Patient has a suitable MSD, volunteer MURD, or KIR mismatched haploidentical donor available in the necessary time for stem cell donation.
  • Patient has any other active malignancy other than the one for which HCT is indicated.
  • Patient had a prior allogeneic HCT
  • Patient had an autologous HCT within the previous 12 months.
  • Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment.
  • Patient is lactating
  • Patient has Down Syndrome
  • Patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the PI.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01328496

Contacts
Contact: Mari H Dallas, MD 1-866-278-5833 info@stjude.org

Locations
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Mari H Dallas, MD    866-278-5833    info@stjude.org   
Principal Investigator: Mari H Dallas, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
The Hartwell Foundation
Assisi Foundation
Investigators
Principal Investigator: Mari H Dallas, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01328496     History of Changes
Other Study ID Numbers: UCBT01
Study First Received: March 31, 2011
Last Updated: March 5, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by St. Jude Children's Research Hospital:
Hematologic Malignancies
Umbilical Cord Blood transplantation
Hematopoietic Cell Transplantation

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on April 21, 2014