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

This study is currently recruiting participants. (see Contacts and Locations)
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
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: 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 July 24, 2014