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

This study has been completed.
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: May 4, 2017
Last verified: March 2017
  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) (10.0 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 Drug: Preparative Regimen Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen

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

Primary Outcome Measures:
  • Event Free Survival (EFS) for Research Participants [ Time Frame: 1 year post-transplant ]
    Estimate EFS for research participants at one-year post transplant by using single unit umbilical cord blood. The event is defined as relapse, graft failure, death due to any cause. The number of participants who did not experience any of those events (relapse, graft failure, death due to any cause) at year 1 post-transplant was given.


Secondary Outcome Measures:
  • Number of Observational Arm Participants Engrafted [ Time Frame: 1 year ]
    For patients enrolled in the observational arm (undergoing a double unit UCBT), the number of patients engrafted was given.

  • Number of Observational Arm Patients Who Relapsed [ Time Frame: 1 year ]
    The number of observational arm patients who relapsed was given.

  • Number of Deaths of Observational Arm Patients [ Time Frame: 1 year ]
    The number of observational arm patients who died was given.

  • Number of Observational Arm Patients With Transplant-related Mortality (TRM) [ Time Frame: First 100 days ]
    The number of patients with TRM within the first 100 days post transplant was given.

  • Number of Participants With Acute GVHD [ Time Frame: 1 year ]
    The number of participants with incidence of acute GVHD by grade was given. Participants are graded on a scale from 1 to 4, with 1 being mild and 4 being severe.

  • Number of Participants With Chronic GVHD [ Time Frame: 1 year ]
    Due to the small sample size, cumulative incidence analysis was not done. The incidence of chronic GVHD was evaluated using NIH Consensus Global Severity Scoring. The number of patients with incidence of chronic GVHD by severity was provided.

  • Time to Engraftment of Research Arm Participants [ Time Frame: first 100 days post transplant ]
    Platelet engraftment was defined as platelet count ≥20,000/mm^3 for 3 consecutive tests performed on different days with no platelet transfusions in the preceding 7 days. Neutrophil engraftment will be defined as achieving ANC ≥ 500/mm3 for 3 consecutive tests performed on different days with evidence of donor cell engraftment. Descriptive statistics are provided.

  • Incidence of Transplant-related Mortality (TRM) [ Time Frame: first 100 days post transplant ]
    TRM is death occurring in patients in continuous complete remission. The numbers of patients with TRM was given.

  • The Number of Participants With Transplant-related Morbidity [ Time Frame: first 100 days post transplant ]
    Any patient who had adverse events listed either as probable or definite in the first 100 days post-transplant are counted as transplant related morbidity. The number of patients with transplant-related morbidity was given.


Enrollment: 14
Actual Study Start Date: June 15, 2011
Study Completion Date: October 31, 2016
Primary Completion Date: October 31, 2016 (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

Drug: 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

Drug: 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   (Child, Adult)
Sexes Eligible for Study:   All
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

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
The Hartwell Foundation
Assisi Foundation
Investigators
Principal Investigator: Amr Qudeimat, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT01328496     History of Changes
Other Study ID Numbers: UCBT01
NCI-2011-03700 ( Registry Identifier: NCI Clinical Trial Registration Program )
Study First Received: March 31, 2011
Results First Received: March 23, 2017
Last Updated: May 4, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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 June 23, 2017