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

Primary Purpose

Hematologic Malignancies, Disorder Related to Transplantation, Hematopoietic Malignancy

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Preparative Regimen

About this trial

This is an interventional treatment trial for Hematologic Malignancies focused on measuring Hematologic Malignancies, Umbilical Cord Blood transplantation, Hematopoietic Cell Transplantation

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Research Arm

Observation Arm

Arm Description

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

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm. Intervention: Preparative Regimen

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Number of Observational Arm Patients Who Relapsed

The number of observational arm patients who relapsed was given.

Number of Deaths of Observational Arm Patients

The number of observational arm patients who died was given.

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.

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.

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.

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.

Incidence of Transplant-related Mortality (TRM)

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

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.

Full Information

NCT ID

NCT01328496

First Posted

March 31, 2011

Last Updated

May 4, 2017

Sponsor

St. Jude Children's Research Hospital

Collaborators

The Hartwell Foundation, Assisi Foundation

1. Study Identification

Unique Protocol Identification Number

NCT01328496

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

June 15, 2011 (Actual)

Primary Completion Date

October 31, 2016 (Actual)

Study Completion Date

October 31, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Jude Children's Research Hospital

Collaborators

The Hartwell Foundation, Assisi Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancies, Disorder Related to Transplantation, Hematopoietic Malignancy

Keywords

Hematologic Malignancies, Umbilical Cord Blood transplantation, Hematopoietic Cell Transplantation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Research Arm

Arm Type

Other

Arm Description

Arm Title

Observation Arm

Arm Type

Other

Arm Description

Patients requiring two UCB units will be eligible for UCBT01 on the observational arm. Intervention: Preparative Regimen

Intervention Type

Drug

Intervention Name(s)

Preparative Regimen

Intervention Description

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.

Primary Outcome Measure Information:

Title

Event Free Survival (EFS) for Research Participants

Description

Time Frame

1 year post-transplant

Secondary Outcome Measure Information:

Title

Number of Observational Arm Participants Engrafted

Description

For patients enrolled in the observational arm (undergoing a double unit UCBT), the number of patients engrafted was given.

Time Frame

1 year

Title

Number of Observational Arm Patients Who Relapsed

Description

The number of observational arm patients who relapsed was given.

Time Frame

1 year

Title

Number of Deaths of Observational Arm Patients

Description

The number of observational arm patients who died was given.

Time Frame

1 year

Title

Number of Observational Arm Patients With Transplant-related Mortality (TRM)

Description

The number of patients with TRM within the first 100 days post transplant was given.

Time Frame

First 100 days

Title

Number of Participants With Acute GVHD

Description

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.

Time Frame

1 year

Title

Number of Participants With Chronic GVHD

Description

Time Frame

1 year

Title

Time to Engraftment of Research Arm Participants

Description

Time Frame

first 100 days post transplant

Title

Incidence of Transplant-related Mortality (TRM)

Description

TRM is death occurring in patients in continuous complete remission. The numbers of patients with TRM was given.

Time Frame

first 100 days post transplant

Title

The Number of Participants With Transplant-related Morbidity

Description

Time Frame

first 100 days post transplant

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Amr Qudeimat, MD

Organizational Affiliation

St. Jude Children's Research Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Jude Children's Research Hospital

City

Memphis

State/Province

Tennessee

ZIP/Postal Code

38105

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.stjude.org

Description

St. Jude Children's Research Hospital

URL

http://www.stjude.org/protocols

Description

Clinical Trials Open at St. Jude

Learn more about this trial

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

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