Clinical trial NCT00354172: Donor Umbilical Cord Blood Natural Killer Cells, Aldesleukin and Umbilical Cord Blood Transplant in Patients With Refractory Hematologic Cancers.
Official title: Transplantation of Umbilical Cord Blood for Myeloid Leukemia Patients Not in CR With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen and UCB NK Cells
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
previously treated myelodysplastic syndromes
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
secondary myelodysplastic syndromes
childhood myelodysplastic syndromes
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2006-07-20
Enrollment: 16
Sex: ALL
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy, natural killer cells, aldesleukin, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal cells and cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, mycophenolate mofetil, and methylprednisolone before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by donor umbilical cord blood natural killer cells, aldesleukin, and umbilical cord blood transplant works in treating patients with refractory hematologic cancer or other diseases.

Detailed description: OBJECTIVES:

Primary

* Determine the incidence of 6-month disease free survival. The primary laboratory objective is the measure of in vivo expansion of umbilical cord blood (UCB) derived natural killer cells (NK) after a fully ablative preparative regimen.

Secondary

* Determine the incidence of transplant-related mortality at 6 months after NK UCB + double UCBT
* Evaluate the pattern of chimerism after NK UCB + double UCBT
* Determine the incidence of neutrophil engraftment at day 42 after NK UCB + double umbilical cord blood transplantation (UCBT)
* Determine the incidence of platelet engraftment at 6 months after NK UCB + double UCBT
* Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after NK UCB + double UCBT
* Determine the incidence of chronic GVHD at 1 year after NK UCB + double UCBT
* Determine the disease-free survival at 1 after NK UCB + double UCBT
* Determine the incidence of relapse at 1 after NK UCB + double UCBT

OUTLINE: This is a single arm, nonrandomized, open-label study.

* Myeloablative conditioning regimen: Patients receive fludarabine intravenously (IV) over 1 hour on days -18 to -16 and cyclophosphamide intravenously (IV) on days -18 and -17. Patients undergo total-body irradiation twice daily on days -16 to -13.
* Haploidentical umbilical cord blood (UCB) natural killer (NK) cell therapy and aldesleukin: Patients undergo haploidentical UCB-enriched NK cell (CD3- depleted) infusion on day -13. Patients then receive aldesleukin subcutaneously on days -13, -11, -9, -7, -5, and -3. Some patients may also receive methylprednisolone IV on days -1 and 0.
* UCB transplantation (UCBT): Patients undergo a single or double UCBT on day 0. Beginning on day 1, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
* Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours 2-3 times daily beginning on day -1 and continuing until day 100, followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily beginning on day -1 and continuing until day 30 (or 7 days after engraftment) in the absence of acute GVHD.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of 1 of the following:

  * Acute myeloid leukemia with active leukemia (i.e., not in complete remission \[CR\]), defined by light microscopy (bone marrow) and having failed ≥ 1 round of standard chemotherapy
  * Chronic myelogenous leukemia with myeloid blast crisis not in second chronic phase after ≥ 1 course of standard chemotherapy and imatinib mesylate
  * Myelodysplastic syndromes (MDS) or other myeloproliferative disorders more than 10% blasts after ≥ 1 course of standard chemotherapy
* Unrelated umbilical cord blood (UCB) donor(s) available - Each unit must be 4-6/6 HLA-A, -B, and -DRB1 matched with the recipient (and to each other if 2 units are utilized) (for UCB graft) AND 3/6 HLA-A, -B, and -DRB1 matched with the recipient (for UCB natural killer \[NK\] cells)
* Karnofsky performance status (PS) 80-100% (adult patients) or Lansky PS 50-100% (pediatric patients)
* Creatinine ≤ 2.0 mg/dL (adult patients) OR creatinine clearance \> 40 mL/min (pediatric patients)
* Bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase ≤ 5 times upper limit of normal (ULN)
* Corrected Carbon Monoxide Diffusing Capacity (DLCO) \> 50% normal OR oxygen saturation \> 92% (in pediatric patients who cannot undergo pulmonary function tests)
* Left ventricular ejection fraction ≥ 45%

Exclusion Criteria:

* Pregnant or nursing
* Positive pregnancy test (Fertile patients must use effective contraception)
* History of HIV infection
* Active infection at time of transplantation

  * Active infection with Aspergillus or other mold within the past 120 days
* Less than 6 months since prior myeloablative transplant (≤ 18 years old)
* Prior myeloablative allotransplant or autologous transplant (\> 18 years old)
* No prior extensive therapy including \> 12 months of any alkylator chemotherapy or \> 6 months of alkylator therapy with extensive radiation (e.g., mantle irradiation for Hodgkin's lymphoma)
* Prior radiation therapy that would make the patient ineligible for total-body irradiation

Primary outcomes:
measure: Number of Participants (Patients) Who Were Disease-free and Alive at 6 Months
timeFrame: 6 Months Post Transplant
Secondary outcomes:
measure: Number of Participants (Patients) Who Were Disease-free and Alive at 12 Months
timeFrame: 12 Months Post transplant
measure: Number of Patients Who Were Disease-free and Alive at 24 Months
timeFrame: 24 Months Post transplant
measure: Number of Participants (Patients) Who Died Due to Transplant.
timeFrame: 6 Months Post Transplant
measure: Number of Participants (Patients) Who Attained Neutrophil Engraftment
timeFrame: Day 42 Post Transplant
measure: Number of Participants (Patients) Who Attained Platelet Engraftment
timeFrame: 1 Year Post Transplant
measure: Number of Participants (Patients) With Acute Graft-versus-host Disease (GVHD) Grade II-IV
timeFrame: Day 100 Post Transplant
measure: Number of Participants (Patients) With Acute Graft-versus-Host Disease at Grade III-IV
timeFrame: Day 100 post transplant
measure: Number of Participants (Patients) With Chronic Graft-Versus-Host Disease
timeFrame: Day 100 through 1 Year Post Transplant
measure: Number of Participants (Patients) Who Died by 12 Months
timeFrame: 1 year Post Transplant
measure: Number of Participants (Patients) Who Died by 24 Months
timeFrame: 2 years post-transplant
measure: Number of Participants (Patients) Who Experienced Relapse by 12 Months
timeFrame: 1 Year Post Transplant
measure: Number of Participants (Patients) Who Experienced Relapse by 24 Months
timeFrame: 2 Years Post transplant
measure: Number of Participants (Patients) With Successful Natural Killer Cell Expansion
timeFrame: 10-13 Days Post Infusion
measure: Chimerism After Double Umbilical Cord Blood Transplant (UCBT)
timeFrame: Day 21, Day 100, 6 Months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Jeffrey Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: