T-Cell Depleted Double UCB for Refractory AML

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Michael Verneris, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01464359
First received: November 1, 2011
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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).


Condition Intervention Phase
Acute Myelogenous Leukemia
Refractory Acute Myelogenous Leukemia
Drug: Allopurinol
Drug: Fludarabine
Radiation: Total body irradiation
Drug: Cyclophosphamide
Drug: Levetiracetam
Drug: Busulfan
Biological: Umbilical Cord Blood Transplantation
Biological: Interleukin-2
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: T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Disease Free Survival [ Time Frame: At 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of Graft Failure [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    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)

  • Incidence of Acute Graft-Versus-Host Disease [ Time Frame: Day 60 ] [ Designated as safety issue: No ]
  • Transplant-Related Mortality [ Time Frame: Day 180 after Transplantation ] [ Designated as safety issue: Yes ]
  • Clinical Disease Response [ Time Frame: 1 Year from Transplantation ] [ Designated as safety issue: No ]
    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.

  • Duration of Survival [ Time Frame: 6 months after Transplantation. ] [ Designated as safety issue: No ]
  • Duration of Survival [ Time Frame: 1 year after Transplantation. ] [ Designated as safety issue: No ]
  • Duration of Survival [ Time Frame: 2 years after Transplantation. ] [ Designated as safety issue: No ]
  • Clinical Disease Response [ Time Frame: 2 Years from Transplantation ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: October 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Allopurinol
On Day 8 pre-transplant, start hydration with allopurinol per standard of care.
Other Name: Zyloprim
Drug: Fludarabine
On Days 7, 6 and 5 pre-transplant, 25 mg/m^2 intravenously over 1 hour.
Other Name: Fludara
Radiation: 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.
Other Name: Radiation
Drug: 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.

Other Name: Cytoxan
Drug: Levetiracetam
Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.
Other Name: Keppra
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
Other Name: Myleran
Biological: 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.
Other Name: UCBT
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.

Other Name: IL-2

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   2 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01464359

Contacts
Contact: Timothy Krepski, RN 612-273-2800 krepsk1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Krepski, RN    612-273-2800    krepsk1@fairview.org   
Principal Investigator: Michael Verneris, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Michael Verneris, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Michael Verneris, Principal Investigator, Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01464359     History of Changes
Other Study ID Numbers: MT2011-15
Study First Received: November 1, 2011
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Masonic Cancer Center, University of Minnesota:
umbilical cord blood transplant

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Allopurinol
Cyclophosphamide
Interleukin-2
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Antimetabolites
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antioxidants
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Free Radical Scavengers
Gout Suppressants
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014