T-Cell Depleted Double UCB for Refractory AML

NCT ID: NCT01464359

Last Updated: 2017-12-28

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2013-10-31

Brief Summary

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This trial is proposes to build on our experience and is designed to maximize early (day 3-14) and late (day 60-71) donor-derived natural killer (NK) cell expansion and function in vivo. The proposed platform will allow us the unique opportunity to compare in vivo function from a transplanted umbilical cord blood (UCB) source (presumed to contain NK progenitors requiring "education" in the recipient).

Detailed Description

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This single center study will determine the feasibility and safety of using a myeloablative conditioning regimen followed (on day 0) by transplantation with double T-cell depleted (TCD) umbilical cord blood (UCB) units where the unit with fewer mononuclear cells (MNCs)/kg will be selected for overnight IL-2 activation prior to infusion. Beginning on day +3, post transplant IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses to expand UCB derived progenitor cells. Post transplant immune suppression prophylaxis will not be administered with the intent to lessen toxicity and allow allogeneic NK cells to function longer providing better anti-leukemic therapy. However if either UCB unit has more than 5% T-cells, the patient will not receive either course of IL-2. Beginning on day +60 after transplantation, a second course of IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses with the purpose of enhancing the in vivo expansion and education of NK cells derived from engrafting UCB cells.

Conditions

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Acute Myelogenous Leukemia Refractory Acute Myelogenous Leukemia

Keywords

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umbilical cord blood transplant

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Allopurinol

Intervention Type DRUG

On Day 8 pre-transplant, start hydration with allopurinol per standard of care.

Fludarabine

Intervention Type DRUG

On Days 7, 6 and 5 pre-transplant, 25 mg/m\^2 intravenously over 1 hour.

Total body irradiation

Intervention Type RADIATION

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.

Cyclophosphamide

Intervention Type DRUG

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.

Levetiracetam

Intervention Type DRUG

Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.

Busulfan

Intervention Type DRUG

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

Umbilical Cord Blood Transplantation

Intervention Type BIOLOGICAL

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.

Interleukin-2

Intervention Type BIOLOGICAL

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.

Interventions

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Allopurinol

On Day 8 pre-transplant, start hydration with allopurinol per standard of care.

Intervention Type DRUG

Fludarabine

On Days 7, 6 and 5 pre-transplant, 25 mg/m\^2 intravenously over 1 hour.

Intervention Type DRUG

Total body irradiation

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.

Intervention Type RADIATION

Cyclophosphamide

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.

Intervention Type DRUG

Levetiracetam

Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.

Intervention Type DRUG

Busulfan

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

Intervention Type DRUG

Umbilical Cord Blood Transplantation

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.

Intervention Type BIOLOGICAL

Interleukin-2

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.

Intervention Type BIOLOGICAL

Other Intervention Names

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Zyloprim Fludara Radiation Cytoxan Keppra Myleran UCBT IL-2

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Verneris, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

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Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

Other Identifiers

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MT2011-15

Identifier Type: -

Identifier Source: org_study_id