- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01464359
T-Cell Depleted Double UCB for Refractory AML
T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia
Study Overview
Status
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Masonic Cancer Center, University of Minnesota
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Aged 2 to 45 years with acute myeloid leukemia (AML) who meet one of the following criteria:
- Primary induction failure defined as no complete remission (CR) after two or three induction cycles (no blast limit).
- Relapsed AML with low disease burden: For patients >21 through 45 years of age: must have <30% marrow blasts within 14 days of enrollment and be at least 28 days from the start of last therapy. For patients 2 through ≤ 21 years of age: must have >5% marrow blasts after no more than 3 induction attempts.
Patients with prior central nervous system (CNS) involvement are eligible provided that it has been treated and is in remission. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocol.
Have acceptable organ function within 14 days of study registration defined as:
- Renal: creatinine ≤ 2.0 mg/dL (adult patients) or calculated creatinine clearance > 40 ml/min (pediatric patients)
- Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 5 times upper limit of normal
- Pulmonary function: diffusing lung capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
- Cardiac: left ventricular ejection fraction ≥ 45%
- Karnofsky Performance Status ≥ 70% (≥ 16 years) or Lansky Play Score ≥ 50 (pediatrics < 16 years)
- Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
- All patients will be questioned about prior exposure to antibody therapy (including OKT3, rituximab, trastuzumab, and gemtuzumab) without affect to eligibility. Patients with prior exposure will have a blood sample collected for human antimouse antibody (HAMA). For patients with no prior antibody therapy exposure, no further action will be taken.
- Voluntary written consent
Exclusion Criteria:
- Active infection at time of enrollment or documented fungal infection within 3 months unless clearance from Infectious Disease
- Evidence of HIV infection or known HIV positive serology
- Pregnant or breast feeding.
- If < or = 21 years old, prior myeloablative transplant within the last 6 months. If > 21 years old prior myeloablative allotransplant or autologous transplant - if prior conditioning regimen included total body irradiation (TBI), then busulfan/cyclophosphamide(BU/CY) prep should be used
- If > 21 years old - extensive prior therapy including > 12 months of any alkylator chemotherapy (etoposide >100 mg/m^2 x 5 days, cyclophosphamide >1 gm/m^2 or mitoxantrone >8 gm/m^2) delivered at 3-4 week intervals or > 6 months alkylator therapy (as above) with extensive radiation (determined by Radiation Oncology, e.g. mantle irradiation for Hodgkin's) and/or prior radiation therapy that makes a patient ineligible for TBI.
- Known hypersensitivity to any of the study agents
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Patients with Acute Myelogenous Leukemia
Patients with chemotherapy refractory Acute Myelogenous Leukemia (AML) after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where the smaller unit is activated overnight in interleukin-2 (IL-2).
IL-2 will be given three times weekly for 6 doses beginning on days+3 and days +60 to expand UCB-derived natural killer (NK) cells in vivo.
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On Day 8 pre-transplant, start hydration with allopurinol per standard of care.
Other Names:
On Days 7, 6 and 5 pre-transplant, 25 mg/m^2 intravenously over 1 hour.
Other Names:
On Days 5, 4, 3, and 2 pre-transplant, 165 cGy times 2 (330 cGy daily, 1320 total dose) according to the University Of Minnesota Blood and Marrow Transplant Program total body irradiation (TBI) guidelines.
Other Names:
On Days 7 and 6 pre-transplant, 60 mg/kg intravenously (IV) over 2 hours with a high volume fluid flush and mesna per institutional guidelines. Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 5, 4, 3 and 2 pre-transplant; 50 mg/kg/day IV over 2 hours.
Other Names:
Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.
Other Names:
Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 9, 8, 7 and 6 pre-transplant; 0.8 mg/kg (1.1 mg/kg if <12 kg) intravenously every 6 hours
Other Names:
Day 0: Two UCB units will compose the graft.
The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit.
The UCB unit without IL-2 activation will be infused first, followed by the IL-2 activated unit.
Both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending.
Other Names:
First Course of IL-2 (begin day +3) post-transplant: For patients ≥ 45 kg, IL-2 will be given at 9 million units every other day for a total of 6 doses subcutaneously. Patients weighing less than 45 kilograms, the IL-2 will be dosed at 5 million units/m^2 every other day for a total of 6 doses. Second Course of IL-2 (day +60): Patients will receive a second course of IL-2 beginning on Day +60 post transplant to expand and educate the NK cells derived from the UCB graft source.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Free Survival
Time Frame: At 3 months
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The primary endpoint is a disease free survival at 3 months in patients with chemotherapy refractory AML after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where one TCD unit is activated overnight in IL-2 followed by the administration of two courses of IL-2 three times a week for 6 doses beginning on day +3 and on day +60 to expand UCB-derived NK cells in vivo.
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At 3 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Graft Failure
Time Frame: Day 42
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Incidence of graft failure defined as an absolute neutrophil count of less than 500/uL and a bone marrow that is less than 5% cellular (marrow aplasia)
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Day 42
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Incidence of Acute Graft-Versus-Host Disease
Time Frame: Day 60
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Day 60
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Transplant-Related Mortality
Time Frame: Day 180 after Transplantation
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Day 180 after Transplantation
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Clinical Disease Response
Time Frame: 1 Year from Transplantation
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Defined as leukemia clearance and complete remission.
Patients will be followed for disease response for 1 year from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only until the resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.
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1 Year from Transplantation
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Duration of Survival
Time Frame: 6 months after Transplantation.
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6 months after Transplantation.
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Duration of Survival
Time Frame: 1 year after Transplantation.
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1 year after Transplantation.
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Duration of Survival
Time Frame: 2 years after Transplantation.
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2 years after Transplantation.
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Clinical Disease Response
Time Frame: 2 Years from Transplantation
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Defined as leukemia clearance and complete remission.
Patients will be followed for disease response for 2 years from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only untilthe resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.
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2 Years from Transplantation
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Collaborators and Investigators
Investigators
- Principal Investigator: Michael Verneris, M.D., Masonic Cancer Center, University of Minnesota
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Analgesics, Non-Narcotic
- Antirheumatic Agents
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Anticonvulsants
- Antioxidants
- Free Radical Scavengers
- Nootropic Agents
- Gout Suppressants
- Cyclophosphamide
- Fludarabine
- Busulfan
- Allopurinol
- Interleukin-2
- Levetiracetam
Other Study ID Numbers
- MT2011-15
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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