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

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.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies; Disorder Related to Transplantation; Hematopoietic Malignancy
• Intervention / Treatment: Drug: Preparative Regimen

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event Free Survival (EFS) for Research Participants	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.	1 year post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Observational Arm Participants Engrafted	For patients enrolled in the observational arm (undergoing a double unit UCBT), the number of patients engrafted was given.	1 year
Number of Observational Arm Patients Who Relapsed	The number of observational arm patients who relapsed was given.	1 year
Number of Deaths of Observational Arm Patients	The number of observational arm patients who died was given.	1 year
Number of Observational Arm Patients With Transplant-related Mortality (TRM)	The number of patients with TRM within the first 100 days post transplant was given.	First 100 days
Number of Participants With Acute GVHD	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.	1 year
Number of Participants With Chronic GVHD	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.	1 year
Time to Engraftment of Research Arm Participants	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.	first 100 days post transplant
Incidence of Transplant-related Mortality (TRM)	TRM is death occurring in patients in continuous complete remission. The numbers of patients with TRM was given.	first 100 days post transplant
The Number of Participants With Transplant-related Morbidity	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.	first 100 days post transplant

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: Assisi Foundation; The Hartwell Foundation
• Investigators: Principal Investigator: Amr Qudeimat, MD, St. Jude Children's Research Hospital

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2011
• Primary Completion (Actual): October 31, 2016
• Study Completion (Actual): October 31, 2016

Study Registration Dates

• First Submitted: March 31, 2011
• First Submitted That Met QC Criteria: March 31, 2011
• First Posted (Estimate): April 4, 2011

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: May 4, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Hematologic Malignancies; Hematopoietic Cell Transplantation; Umbilical Cord Blood transplantation
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: UCBT01; NCI-2011-03700 (Registry Identifier: NCI Clinical Trial Registration Program)

Drug and device information, study documents

• 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