LeukemiaPhase 2NCT00354172
Donor Umbilical Cord Blood Natural Killer Cells, Aldesleukin and Umbilical Cord Blood Transplant in Patients With Refractory Hematologic Cancers.
A Phase 2 study testing aldesleukin, filgrastim and natural killer cell (NK) therapy in people with Leukemia and Myelodysplastic Syndromes, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 45 years
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- aldesleukin, filgrastim and natural killer cell (NK) therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to Aug 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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%
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
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
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.
Read the 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
- Being tested
- aldesleukin, filgrastim, natural killer cell (NK) therapy, cyclophosphamide, cyclosporine
- 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
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Congenital Abnormalities, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
aldesleukinBiological
Also called IL-2, interleukin-2
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
filgrastimBiological
Also called granulocyte colony-stimulating factor (G-CSF)
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.
natural killer cell (NK) therapyBiological
Also called NK cells
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.
cyclophosphamideDrug
Also called Cytoxan
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)
cyclosporineDrug
Also called cyclosporin
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 called Fludara
Fludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -18 to -16)
Also called Medrol, Solu-Medrol, Depo-Medrol, methylprednisolone sodium succinate
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 called mycophenolic acid
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).
Umbilical Cord Blood Transplantation (UCBT)Procedure or surgery
Also called allogeneic transplant
The product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter.
Total body irradiation (TBI)Radiation
Also called radiation
TBI 165 Gray (cGy) will be given twice daily for a total dose of 1320 cGy (days
-16 to -13).
| Study group | Role | What they receive |
|---|---|---|
| Treated Patients | Experimental | All patients receiving treatment with chemotherapy and radiation, along with natural killer cells, aldesleukin and umbilical cord blood transplant. Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 Months Post Transplant
Secondary outcomes (14)
Number of Participants (Patients) Who Were Disease-free and Alive at 12 Months
Number of patients who were alive and free of disease (malignancy) at 12 months after transplant.
Measured: 12 Months Post transplant
Number of Patients Who Were Disease-free and Alive at 24 Months
Number of patients who were alive and free of disease (malignancy) at 24 months after transplant.
Measured: 24 Months Post transplant
Number of Participants (Patients) Who Died Due to Transplant.
Patients who had transplant-related mortality (TRM). TRM = adverse event(s) that occur(s) after the patient has received a transplant, the principal investigator decides it is related to the procedure and the patient dies within 6 months.
Measured: 6 Months Post Transplant
Number of Participants (Patients) Who Attained Neutrophil Engraftment
Defined as absolute neutrophils (ANC) > 5 x 10^8/Liter for 3 consecutive days.
ANC is the real number of white blood cells (WBCs) that are neutrophils. The absolute neutrophil count is commonly called the ANC. The ANC is not measured directly. It is derived by multiplying the WBC count times the percent of neutrophils in the differential WBC count. The percent of neutrophils consists of the segmented (fully mature) neutrophils) + the bands (almost mature neutrophils). The normal range for the ANC = 1.5 to 8.0 (1,500 to 8,000/mm3).
Measured: Day 42 Post Transplant
Number of Participants (Patients) Who Attained Platelet Engraftment
Platelet engraftment is defined as platelet counts > 50 x 10^9/Liter for 3 consecutive days.
Measured: 1 Year Post Transplant
Number of Participants (Patients) With Acute Graft-versus-host Disease (GVHD) Grade II-IV
Graft-versus-host disease (GVHD) is a common complication of transplantation in which functional immune cells in the transplanted marrow recognize the recipient as foreign and mount an immunologic attack. The acute or fulminant form of the disease (aGVHD) is normally observed within the first 100 days post-transplant, and is a major challenge to transplants owing to associated morbidity and mortality. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of I to a high of IV. Patients with grade IV GVHD usually have a poor prognosis.
Measured: Day 100 Post Transplant
Number of Participants (Patients) With Acute Graft-versus-Host Disease at Grade III-IV
Graft-versus-host disease (GVHD) is a common complication of transplantation in which functional immune cells in the transplanted marrow recognize the recipient as foreign and mount an immunologic attack. The acute or fulminant form of the disease (aGVHD) is normally observed within the first 100 days post-transplant, and is a major challenge to transplants owing to associated morbidity and mortality. Acute GVHD is staged as follows: overall grade (skin-liver-gut) with each organ staged individually from a low of I to a high of IV. Patients with grade IV GVHD usually have a poor prognosis.
Measured: Day 100 post transplant
Number of Participants (Patients) With Chronic Graft-Versus-Host Disease
The chronic form of graft-versus-host-disease (cGVHD) normally occurs after 100 days. The appearance of moderate to severe cases of cGVHD adversely influences long-term survival.
Measured: Day 100 through 1 Year Post Transplant
Number of Participants (Patients) Who Died by 12 Months
Number of patients who died after receiving treatment within 12 months post transplant.
Measured: 1 year Post Transplant
Number of Participants (Patients) Who Died by 24 Months
Number of patients who died after receiving treatment within 24 months post transplant.
Measured: 2 years post-transplant
Number of Participants (Patients) Who Experienced Relapse by 12 Months
Number of patients who experienced recurrence or progression of disease from the time of transplant.
Measured: 1 Year Post Transplant
Number of Participants (Patients) Who Experienced Relapse by 24 Months
Number of patients who experienced recurrence or progression of disease from the time of transplant.
Measured: 2 Years Post transplant
Number of Participants (Patients) With Successful Natural Killer Cell Expansion
Defined by an absolute circulating donor-derived natural killer cell count of >100 cells/microliter 10-13 days after infusion with <5% donor T and B cells in the mononuclear population
Measured: 10-13 Days Post Infusion
Chimerism After Double Umbilical Cord Blood Transplant (UCBT)
Calculation of Median (range) of percentage of donor cells engrafted (present) in the recipient (patient).
Measured: Day 21, Day 100, 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2006 (estimated)
- Study startFeb 2006
- Primary completionAug 2008
- Study completionAug 2008
Why it stopped: Competing study was started.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Masonic Cancer Center, University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey Miller, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00354172
- Sponsor's protocol ID
- UMN-2005LS058
- Other IDs
- MT2005-18, 0509M73449
- Status last verified
- Dec 2017
- First submitted
- 19 Jul 2006
- Last updated
- 28 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00354172
- Acronym / sponsor ID
- UMN-2005LS058
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Competing study was started.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Feb 2006
- Primary completion
- Aug 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 20 Jul 2006 (estimated)
- Results
- Posted 31 Dec 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treated Patients | Experimental | 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)All patients receiving treatment with chemotherapy and radiation, along with natural killer cells, aldesleukin and umbilical cord blood transplant. |
Who may qualify
- Ages
- Up to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Diagnosis of 1 of the following:
- 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)
Key exclusion criteria (9 listed)
- Pregnant or nursing
- Positive pregnancy test (Fertile patients must use effective contraception)
- History of HIV infection
- Active infection at time of transplantation
- Less than 6 months since prior myeloablative transplant (≤ 18 years old)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| aldesleukinAlso: IL-2, interleukin-210 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 | Treated Patients |
| filgrastimAlso: granulocyte colony-stimulating factor (G-CSF)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 | Treated Patients |
| natural killer cell (NK) therapyAlso: NK cellsAll 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. | Biological | Treated Patients |
| cyclophosphamideAlso: CytoxanCyclophosphamide 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 | Treated Patients |
| cyclosporineAlso: cyclosporinPatients 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 | Treated Patients |
| fludarabine phosphateAlso: FludaraFludarabine 25 mg/m2/day intravenously (IV) x 3 days, total dose 75 mg/m2 (days -18 to -16) | Drug | Treated Patients |
| methylprednisoloneAlso: Medrol, Solu-Medrol, Depo-Medrol, methylprednisolone sodium succinateThis 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 | Treated Patients |
| mycophenolate mofetilAlso: mycophenolic acidAll 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). | Drug | Treated Patients |
| Umbilical Cord Blood Transplantation (UCBT)Also: allogeneic transplantThe product is infused via intravenous (IV) drip directly into the central line without a needle, pump or filter. | Procedure or surgery | Treated Patients |
| Total body irradiation (TBI)Also: radiationTBI 165 Gray (cGy) will be given twice daily for a total dose of 1320 cGy (days -16 to -13). | Radiation | Treated Patients |
Primary outcome
Number of Participants (Patients) Who Were Disease-free and Alive at 6 Months
Time frame: 6 Months Post Transplant
Number of patients who were alive and free of disease (malignancy) at 6 months after transplant.
14 secondary outcomes
Number of Participants (Patients) Who Were Disease-free and Alive at 12 Months
Time frame: 12 Months Post transplant
Number of Patients Who Were Disease-free and Alive at 24 Months
Time frame: 24 Months Post transplant
Number of Participants (Patients) Who Died Due to Transplant.
Time frame: 6 Months Post Transplant
Number of Participants (Patients) Who Attained Neutrophil Engraftment
Time frame: Day 42 Post Transplant
Number of Participants (Patients) Who Attained Platelet Engraftment
Time frame: 1 Year Post Transplant
Number of Participants (Patients) With Acute Graft-versus-host Disease (GVHD) Grade II-IV
Time frame: Day 100 Post Transplant
Number of Participants (Patients) With Acute Graft-versus-Host Disease at Grade III-IV
Time frame: Day 100 post transplant
Number of Participants (Patients) With Chronic Graft-Versus-Host Disease
Time frame: Day 100 through 1 Year Post Transplant
Number of Participants (Patients) Who Died by 12 Months
Time frame: 1 year Post Transplant
Number of Participants (Patients) Who Died by 24 Months
Time frame: 2 years post-transplant
Number of Participants (Patients) Who Experienced Relapse by 12 Months
Time frame: 1 Year Post Transplant
Number of Participants (Patients) Who Experienced Relapse by 24 Months
Time frame: 2 Years Post transplant
Number of Participants (Patients) With Successful Natural Killer Cell Expansion
Time frame: 10-13 Days Post Infusion
Chimerism After Double Umbilical Cord Blood Transplant (UCBT)
Time frame: Day 21, Day 100, 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Miller, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing aldesleukin, filgrastim and natural killer cell (NK) therapy in people with Leukemia and Myelodysplastic Syndromes, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants (Patients) Who Were Disease-free and Alive at 6 Months (time frame: 6 Months Post Transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2017.