NCT00354172

Donor Umbilical Cord Blood Natural Killer Cells, Aldesleukin and Umbilical Cord Blood Transplant in Patients With Refractory Hematologic Cancers.

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

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: Masonic Cancer Center, University of Minnesota · Academic / Other
• Sex: All
• Age: 45 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Leukemia
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
BIOLOGICAL	aldesleukin	10 Million units subcutaneous every other day on days -13 (after Natural killer cell graft), -11, -9, -7, -5, -3) If \< 45 kilograms (Kg) - interleukin (IL)-2 at 5 MU/m2
BIOLOGICAL	filgrastim	All patients will receive filgrastim (same as granulocyte-colony stimulating factor or G-CSF) 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight beginning on day +1 after umbilical cord blood (UCB) infusion. Granulocyte Colony Stimulating Factor (G-CSF) will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10\^9/L for three consecutive days and then discontinued. If the ANC decreases to \<1.0 x 10\^9/L, G-CSF will be reinstituted.
BIOLOGICAL	natural killer cell (NK) therapy	All CD3 depleted cells will be given (less those required for product monitoring). The minimum size of a starting NK cell unit will be 700 million mononuclear cells before processing. NK cells (CD56+) and NK cell precursors (CD34+/CD7-, CD34+/CD7+, CD34-/CD7+) will be monitored and reported but will not serve as lot release.
DRUG	cyclophosphamide	Cyclophosphamide to be administered with high volume fluid flush and mesna on days-18 and -17 after fludarabine. Cyclophosphamide 60 mg/kg/day intravenously (IV) x 2 days, total dose 120 mg/m2 (days -18 and -17)
DRUG	cyclosporine	Patients will receive cyclosporine (CSA) therapy beginning on day -1 maintaining a level of \>200 ng/mL. For adults the initial dose will be 2.5 mg/kg intravenously (IV) over 2 hours every 12 hours. For children \<40 kg the initial dose will be 2.5 mg/kg IV over 2 hours every 8 hours.
DRUG	fludarabine phosphate	Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -18 to -16)
DRUG	methylprednisolone	This modification will be enacted based on the engraftment stopping rule on all subsequent patients to stop natural killer (NK) cell reaction. Methylprednisolone bolus 1000 mg intravenously (IV) will be administered day -1 and day 0 (before umbilical cord blood transplant) to suppress natural killer (NK) cell activity before transplant. Starting cyclosporin and mycophenolate mofetil (MMF) will also contribute to suppressing residual NK cell activity.
DRUG	mycophenolate mofetil	All patients will begin mycophenolate mofetil (MMF) on day -1. Patients ≥ 45 kilograms will receive MMF at the dose of 3 grams/day divided into 2 or 3 doses. Pediatric patient (\<45 kilograms) will receive MMF at the dose of 15 mg/kg. Use intravenous (IV) route between days -1 and +5, then, if tolerated, may change to by mouth (PO) between days +6 and +30. Stop MMF at day +30 or 7 days after engraftment, whichever day is later, if no acute Graft Versus Host Disease. (Definition of engraftment is 1st day of 3 consecutive days of absolute neutrophil count \[ANC\] \> 0.5 x 10\^9 /L).
PROCEDURE	Umbilical Cord Blood Transplantation (UCBT)	The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.
RADIATION	Total body irradiation (TBI)	TBI 165 Gray (cGy) will be given twice daily for a total dose of 1320 cGy (days -16 to -13).

Timeline

• Start date: 2006-02-01
• Primary completion: 2008-08-01
• Completion: 2008-08-01
• First posted: 2006-07-20
• Last updated: 2017-12-28
• Results posted: 2009-12-31

Locations

1 site across 1 country: United States