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

NCT ID: NCT01328496

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-15
• Study Completion Date: 2016-10-31

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.

Conditions

Hematologic Malignancies; Disorder Related to Transplantation; Hematopoietic Malignancy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: OTHER

Preparative Regimen

Intervention Type: DRUG

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

Group Type: OTHER

Preparative Regimen

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Hartwell Foundation

OTHER

Sponsor Role: collaborator

Assisi Foundation

OTHER

Sponsor Role: collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Amr Qudeimat, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Countries

United States

Related Links

http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

NCI-2011-03700

Identifier Type: REGISTRY

Identifier Source: secondary_id

UCBT01

Identifier Type: -

Identifier Source: org_study_id