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

NCT00354172 | Terminated Phase 2 Results DMC

• 3 other identifiers: UMN-2005LS058MT2005-180509M73449
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants (Patients) Who Were Disease-free and Alive at 6 Months

  Number of patients who were alive and free of disease (malignancy) at 6 months after transplant.

  6 Months Post Transplant

Secondary Outcomes (14)

• Number of Participants (Patients) Who Were Disease-free and Alive at 12 Months

  12 Months Post transplant

• Number of Patients Who Were Disease-free and Alive at 24 Months

  24 Months Post transplant

• Number of Participants (Patients) Who Died Due to Transplant.

  6 Months Post Transplant

• Number of Participants (Patients) Who Attained Neutrophil Engraftment

  Day 42 Post Transplant

• Number of Participants (Patients) Who Attained Platelet Engraftment

  1 Year Post Transplant

Study Arms (1)

Treated Patients

EXPERIMENTAL

All patients receiving treatment with chemotherapy and radiation, along with natural killer cells, aldesleukin and umbilical cord blood transplant.

Biological: aldesleukin; Biological: filgrastim; Biological: natural killer cell (NK) therapy; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methylprednisolone; Drug: mycophenolate mofetil; Procedure: Umbilical Cord Blood Transplantation (UCBT); Radiation: Total body irradiation (TBI)

Interventions

aldesleukin BIOLOGICAL

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

Also known as: IL-2, interleukin-2

Treated Patients

filgrastim BIOLOGICAL

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.

Also known as: granulocyte colony-stimulating factor (G-CSF)

Treated Patients

natural killer cell (NK) therapy BIOLOGICAL

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.

Also known as: NK cells

Treated Patients

cyclophosphamide DRUG

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)

Also known as: Cytoxan

Treated Patients

cyclosporine DRUG

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.

Also known as: cyclosporin

Treated Patients

fludarabine phosphate DRUG

Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -18 to -16)

Also known as: Fludara

Treated Patients

methylprednisolone DRUG

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.

Also known as: Medrol, Solu-Medrol, Depo-Medrol, methylprednisolone sodium succinate

Treated Patients

mycophenolate mofetil DRUG

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).

Also known as: mycophenolic acid

Treated Patients

Umbilical Cord Blood Transplantation (UCBT) PROCEDURE

The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.

Also known as: allogeneic transplant

Treated Patients

Total body irradiation (TBI) RADIATION

TBI 165 Gray (cGy) will be given twice daily for a total dose of 1320 cGy (days -16 to -13).

Also known as: radiation

Treated Patients

Eligibility Criteria

• Age: Up to 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Blast Crisis; Leukemia, Myeloid, Acute

Interventions

aldesleukin; Interleukin-2; Filgrastim; Granulocyte Colony-Stimulating Factor; Therapeutics; Cyclophosphamide; Cyclosporine; fludarabine phosphate; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate; Mycophenolic Acid; Cord Blood Stem Cell Transplantation; Transplantation, Homologous; Whole-Body Irradiation; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques; Physical Phenomena

Results Point of Contact

• Title: Jeffrey Miller, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

mille011@umn.edu

612-625-7409

Study Officials

• Jeffrey Miller, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2006
• First Posted: July 20, 2006
• Study Start: February 1, 2006
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: December 28, 2017
• Results First Posted: December 31, 2009

Record last verified: 2017-12

Locations

US (1)