Clinical trial NCT01464359: T-Cell Depleted Double UCB for Refractory AML
Official title: T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myelogenous Leukemia
Refractory Acute Myelogenous Leukemia
Keywords: umbilical cord blood transplant
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2011-11-03
Enrollment: 3
Sex: ALL
Minimum age (years): 2
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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 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

Primary outcomes:
measure: Disease Free Survival
timeFrame: At 3 months
Secondary outcomes:
measure: Incidence of Graft Failure
timeFrame: Day 42
measure: Incidence of Acute Graft-Versus-Host Disease
timeFrame: Day 60
measure: Transplant-Related Mortality
timeFrame: Day 180 after Transplantation
measure: Clinical Disease Response
timeFrame: 1 Year from Transplantation
measure: Duration of Survival
timeFrame: 6 months after Transplantation.
measure: Duration of Survival
timeFrame: 1 year after Transplantation.
measure: Duration of Survival
timeFrame: 2 years after Transplantation.
measure: Clinical Disease Response
timeFrame: 2 Years from Transplantation
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Michael Verneris, M.D.
role: PRINCIPAL_INVESTIGATOR
References: