Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen
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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)(13.2 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 165 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 |
Genetic: Preparative Regimen |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen |
- Event Free survival at one- year post transplant will be estimated for research participants by using single unit umbilical cord blood [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]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).
- The clinical outcome of patients undergoing a double unit UCBT will be described by engraftment, relapse/death status [ Time Frame: 1 year ] [ Designated as safety issue: No ]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.
- The incidence and severity of acute and chronic GVHD of patients enrolled in the research arm will be estimated . [ Time Frame: 1 years ] [ Designated as safety issue: No ]The cumulative incidence of acute and chronic GVHD will be estimated using Gray's method and death is the competing risk event.
- Time to neutrophil and platelet engraftment as well as the incidence of engraftment among patients enrolled in the research arm will be estimated. method [ Time Frame: 1 year ] [ Designated as safety issue: No ]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 .
- 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 . [ Time Frame: 1 year ] [ Designated as safety issue: No ]The cumulative incidence of TRM and transplant related morbidity will be estimated .TRM is death occurring in patients in continuous complete remission.
| Estimated Enrollment: | 43 |
| Study Start Date: | June 2011 |
| Estimated Study Completion Date: | June 2020 |
| Estimated Primary Completion Date: | June 2020 (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 |
Genetic: Preparative Regimen
Fludarabine (75 mg/m2), fractionated total body irradiation (TBI)(13.2 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 165 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 |
Genetic: Preparative Regimen
Fludarabine (75 mg/m2), fractionated total body irradiation (TBI)(13.2 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 165 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.
- Characterize the pharmacokinetics of mycophenolate mofetil (MMF).
Eligibility| Ages Eligible for Study: | up to 21 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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| Contact: Mari H Dallas, MD | 1-866-278-5833 | info@stjude.org |
| United States, Tennessee | |
| St. Jude Children's Research Hospital | Recruiting |
| Memphis, Tennessee, United States, 38105 | |
| Contact: Mari H Dallas, MD 866-278-5833 info@stjude.org | |
| Principal Investigator: Mari H Dallas, MD | |
| Principal Investigator: | Mari H Dallas, MD | St. Jude Children's Research Hospital |
More Information
Additional Information:
No publications provided
| Responsible Party: | St. Jude Children's Research Hospital |
| ClinicalTrials.gov Identifier: | NCT01328496 History of Changes |
| Other Study ID Numbers: | UCBT01 |
| Study First Received: | March 31, 2011 |
| Last Updated: | January 25, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
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 18, 2013