Chemotherapy, Total-Body Irradiation, Donor Natural Killer Cell Infusion, Aldesleukin, and UCB Transplant in Treating Patients With Relapsed or Refractory AML

NCT00871689 | Terminated Phase 2 Results DMC

• 3 other identifiers: 2008LS110MT2008-360810M51781
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells and natural killer 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. Giving interleukin-2 (IL-2, aldesleukin) after transplant may stimulate the natural killer cells to kill any remaining cancer cells. PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with total-body irradiation followed by interleukin-2 (IL-2, aldesleukin), and umbilical cord blood transplant and to see how well it works in treating patients with relapsed or refractory acute myeloid leukemia.

Conditions

Leukemia

Keywords

recurrent adult acute myeloid leukemia; 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); recurrent childhood acute myeloid leukemia; secondary acute myeloid leukemia; childhood acute myeloid leukemia with 11q23 (MLL) abnormalities; childhood acute myeloid leukemia with inv(16)(p13;q22); childhood acute myeloid leukemia with t(15;17)(q22;q12); childhood acute myeloid leukemia with t(16;16)(p13;q22); childhood acute myeloid leukemia with t(8;21)(q22;q22)

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Neutrophil Engraftment

  Number of patient with absolute neutrophils \>500\*10\^8/kg by 42 days post transplant.

  Day 42

• Number of Patients With Grade III-IV Acute Graft-Versus-Host (GVHD) Disease

  Number of patients with Grade III-IV GVHD. Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted material attacks the transplant recipient's body. Acute GVHD usually happens within the first 3 months after transplant.

  Day 100 Post Transplant

Secondary Outcomes (6)

• Incidence of Primary Graft Failure

  Day 42

• Number of Patients With Acute Graft-Versus-Host (GVHD) Disease

  Day 100 Post Transplant

• Number of Patients With Transplant-Related Death (TRD)

  1 Year Post Transplant

• Number of Patients With Complete Remission of Disease

  Day 100

• Median Overall Survival

  Month 6

Study Arms (1)

UCBT With Post-Transplant IL-2

EXPERIMENTAL

Patients receive cyclophosphamide, fludarabine phosphate, total-body irradiation, T cell depleted umbilical cord blood transplantation (UCBT), followed by interleukin-2 (IL-2, aldesleukin) every other day beginning day +3 for a total of 6 doses and again on day +60 every other day for 6 doses.

Biological: aldesleukin; Drug: cyclophosphamide; Drug: fludarabine phosphate; Procedure: umbilical cord blood transplantation; Radiation: total-body irradiation

Interventions

aldesleukin BIOLOGICAL

IL-2 will be administered (9 million units; 5 million units if weight is less than 45 kg) every other day beginning on day +3 for a total of 6 doses and again on day +60 every other day for 6 doses.

Also known as: IL-2, interleukin-2

UCBT With Post-Transplant IL-2

cyclophosphamide DRUG

60 mg/kg over 1 hour intravenously (IV) on days -7 and -6.

Also known as: Cytoxan

UCBT With Post-Transplant IL-2

fludarabine phosphate DRUG

25 mg/m\^2 intravenously (IV) over 1 hour on days -7 through -5.

Also known as: Fludarabine, Fludara

UCBT With Post-Transplant IL-2

umbilical cord blood transplantation PROCEDURE

On day 0, transplantation will occur with double T-cell depleted (TCD) umbilical cord blood (UCB) units

Also known as: UCBT

UCBT With Post-Transplant IL-2

total-body irradiation RADIATION

administered on days -5 through -2; 330 cGy daily

Also known as: TBI

UCBT With Post-Transplant IL-2

Eligibility Criteria

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

You may qualify if:

• Aged 0 to 45 years 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 acute myeloid leukemia (AML) with low disease burden
• For patients 19 through 45 years of age: must have less than 10% marrow blasts at time of enrollment for patients who did not receive re-induction or measured at least 28 days from the start of re-induction therapy. Patients who have relapsed more than 12 months following a prior hematopoietic cell transplant (HCT) and did not reach CR following one re-induction cycle but have less than 10% marrow blasts are eligible.
• For patients 0 through 18 years of age: must have less than 50% marrow blasts after no more than 3 induction attempts
• CR3 or greater. This will include CRp defined as CR without platelet recovery to 100,000/mcL.
• CR1 or CR2 with high risk features (therapy induced, prior myelodysplastic syndrome (MDS) or myeloproliferative disease (MPD), high risk cytogenetic or molecular phenotype) with no available alternate (sibling, URD or UCB) donors.
• 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 enrollment defined as:
• Renal: creatinine ≤ 2.0 mg/dL (adult patients) or calculated creatinine clearance \> 40 ml/min (pediatric patients)
• Hepatic: bilirubin, AST/ALT, ALP ≤ 5 x upper limit of normal
• Pulmonary function: DLCOcorr \> 50% of normal, (oxygen saturation \[\>92%\] can be used in child where PFT's cannot be obtained)
• Cardiac: left ventricular ejection fraction ≥ 45%
• Karnofsky score (adults) \> 70% or Lansky score \> 50% (pediatrics)
• 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.

You may not qualify if:

• Active infection at time of enrollment or documented fungal infection within 3 months
• Evidence of HIV infection or known HIV positive serology
• Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
• If ≤ 18 years old, prior myeloablative transplant within the last 6 months. If \> 18 years old prior myeloablative allotransplant or autologous transplant
• 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 total body irradiation (TBI).
• Criteria for Second Course of IL-2 (begin day +60):
• No Graft-Versus-Host Disease (GVHD), active infection or any other severe medical co-morbidity
• Absolute neutrophil count (ANC) \> 1000 without growth factor support
• No grade 4 toxicity (except fevers) attributed to IL-2 during course #1

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

University of Minnesota Children's Hospital - Fairview

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Congenital Abnormalities

Interventions

aldesleukin; Interleukin-2; Cyclophosphamide; fludarabine phosphate; fludarabine; Cord Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Limitations and Caveats

Quantitative, phenotypic and functional assessment of the in vivo expanded UCB-derived NK cells on Day 72 were not performed. Patients were not well enough to provide research samples.

Results Point of Contact

• Title: Michael Verneris, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

verneris@umn.edu

612-626-2961

Study Officials

• Michael R. Verneris, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: March 27, 2009
• First Posted: March 30, 2009
• Study Start: January 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: October 1, 2011
• Last Updated: December 28, 2017
• Results First Posted: July 16, 2012

Record last verified: 2017-12

Locations

US (1)