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

Hematologic Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01328496
• Other study ID #: UCBT01
• Secondary ID: NCI-2011-03700
• Status: Completed
• Phase: Phase 2
• First received: March 31, 2011
• Last updated: February 8, 2017
• Start date: June 15, 2011
• Est. completion date: October 31, 2016

Study information

• Verified date: February 2017
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: October 31, 2016
• Est. primary completion date: October 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disorder Related to Transplantation
• Hematologic Malignancies
• Hematologic Neoplasms
• Hematopoietic Malignancy
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (3)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	Assisi Foundation, The Hartwell Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free survival at one- year post transplant will be estimated for research participants by using single unit umbilical cord blood	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).	1 year
Secondary	The clinical outcome of patients undergoing a double unit UCBT will be described by engraftment, relapse/death status	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.	1 year
Secondary	The incidence and severity of acute and chronic GVHD of patients enrolled in the research arm will be estimated .	The cumulative incidence of acute and chronic GVHD will be estimated using Gray's method and death is the competing risk event.	1 years
Secondary	Time to neutrophil and platelet engraftment as well as the incidence of engraftment among patients enrolled in the research arm will be estimated. method	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 .	1 year
Secondary	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 .	The cumulative incidence of TRM and transplant related morbidity will be estimated .TRM is death occurring in patients in continuous complete remission.	1 year

External Links

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