T-Cell Depleted Double UCB for Refractory AML

NCT01464359 | Terminated Phase 2 Results

• 1 other identifier: MT2011-15
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is proposes to build on our experience and is designed to maximize early (day 3-14) and late (day 60-71) donor-derived natural killer (NK) cell expansion and function in vivo. The proposed platform will allow us the unique opportunity to compare in vivo function from a transplanted umbilical cord blood (UCB) source (presumed to contain NK progenitors requiring "education" in the recipient).

Conditions

Acute Myelogenous Leukemia; Refractory Acute Myelogenous Leukemia

Keywords

umbilical cord blood transplant

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  The primary endpoint is a disease free survival at 3 months in patients with chemotherapy refractory AML after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where one TCD unit is activated overnight in IL-2 followed by the administration of two courses of IL-2 three times a week for 6 doses beginning on day +3 and on day +60 to expand UCB-derived NK cells in vivo.

  At 3 months

Secondary Outcomes (8)

• Incidence of Graft Failure

  Day 42

• Incidence of Acute Graft-Versus-Host Disease

  Day 60

• Transplant-Related Mortality

  Day 180 after Transplantation

• Clinical Disease Response

  1 Year from Transplantation

• Duration of Survival

  6 months after Transplantation.

Study Arms (1)

Patients with Acute Myelogenous Leukemia

EXPERIMENTAL

Patients with chemotherapy refractory Acute Myelogenous Leukemia (AML) after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where the smaller unit is activated overnight in interleukin-2 (IL-2). IL-2 will be given three times weekly for 6 doses beginning on days+3 and days +60 to expand UCB-derived natural killer (NK) cells in vivo.

Drug: Allopurinol; Drug: Fludarabine; Radiation: Total body irradiation; Drug: Cyclophosphamide; Drug: Levetiracetam; Drug: Busulfan; Biological: Umbilical Cord Blood Transplantation; Biological: Interleukin-2

Interventions

Allopurinol DRUG

On Day 8 pre-transplant, start hydration with allopurinol per standard of care.

Also known as: Zyloprim

Patients with Acute Myelogenous Leukemia

Fludarabine DRUG

On Days 7, 6 and 5 pre-transplant, 25 mg/m\^2 intravenously over 1 hour.

Also known as: Fludara

Patients with Acute Myelogenous Leukemia

Total body irradiation RADIATION

On Days 5, 4, 3, and 2 pre-transplant, 165 cGy times 2 (330 cGy daily, 1320 total dose) according to the University Of Minnesota Blood and Marrow Transplant Program total body irradiation (TBI) guidelines.

Also known as: Radiation

Patients with Acute Myelogenous Leukemia

Cyclophosphamide DRUG

On Days 7 and 6 pre-transplant, 60 mg/kg intravenously (IV) over 2 hours with a high volume fluid flush and mesna per institutional guidelines. Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 5, 4, 3 and 2 pre-transplant; 50 mg/kg/day IV over 2 hours.

Also known as: Cytoxan

Patients with Acute Myelogenous Leukemia

Levetiracetam DRUG

Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.

Also known as: Keppra

Patients with Acute Myelogenous Leukemia

Busulfan DRUG

Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 9, 8, 7 and 6 pre-transplant; 0.8 mg/kg (1.1 mg/kg if \<12 kg) intravenously every 6 hours

Also known as: Myleran

Patients with Acute Myelogenous Leukemia

Umbilical Cord Blood Transplantation BIOLOGICAL

Day 0: Two UCB units will compose the graft. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. The UCB unit without IL-2 activation will be infused first, followed by the IL-2 activated unit. Both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending.

Also known as: UCBT

Patients with Acute Myelogenous Leukemia

Interleukin-2 BIOLOGICAL

First Course of IL-2 (begin day +3) post-transplant: For patients ≥ 45 kg, IL-2 will be given at 9 million units every other day for a total of 6 doses subcutaneously. Patients weighing less than 45 kilograms, the IL-2 will be dosed at 5 million units/m\^2 every other day for a total of 6 doses. Second Course of IL-2 (day +60): Patients will receive a second course of IL-2 beginning on Day +60 post transplant to expand and educate the NK cells derived from the UCB graft source.

Also known as: IL-2

Patients with Acute Myelogenous Leukemia

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged 2 to 45 years with acute myeloid leukemia (AML) 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 AML with low disease burden: For patients \>21 through 45 years of age: must have \<30% marrow blasts within 14 days of enrollment and be at least 28 days from the start of last therapy. For patients 2 through ≤ 21 years of age: must have \>5% marrow blasts after no more than 3 induction attempts.
• 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 study registration defined as:
• Renal: creatinine ≤ 2.0 mg/dL (adult patients) or calculated creatinine clearance \> 40 ml/min (pediatric patients)
• Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 5 times upper limit of normal
• Pulmonary function: diffusing lung capacity for carbon monoxide corrected for hemoglobin (DLCOcorr) \> 50% of normal, (oxygen saturation \[\>92%\] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
• Cardiac: left ventricular ejection fraction ≥ 45%
• Karnofsky Performance Status ≥ 70% (≥ 16 years) or Lansky Play Score ≥ 50 (pediatrics \< 16 years)
• 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.
• All patients will be questioned about prior exposure to antibody therapy (including OKT3, rituximab, trastuzumab, and gemtuzumab) without affect to eligibility. Patients with prior exposure will have a blood sample collected for human antimouse antibody (HAMA). For patients with no prior antibody therapy exposure, no further action will be taken.
• Voluntary written consent

You may not qualify if:

• Active infection at time of enrollment or documented fungal infection within 3 months unless clearance from Infectious Disease
• Evidence of HIV infection or known HIV positive serology
• Pregnant or breast feeding.
• If \< or = 21 years old, prior myeloablative transplant within the last 6 months. If \> 21 years old prior myeloablative allotransplant or autologous transplant - if prior conditioning regimen included total body irradiation (TBI), then busulfan/cyclophosphamide(BU/CY) prep should be used
• If \> 21 years old - 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 TBI.
• Known hypersensitivity to any of the study agents

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Allopurinol; fludarabine; fludarabine phosphate; Whole-Body Irradiation; Radiation; Cyclophosphamide; Levetiracetam; Busulfan; Cord Blood Stem Cell Transplantation; Interleukin-2

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Physical Phenomena; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Acetamides; Amides; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Michael R Verneris
• Organization: University of Minnesota, Pediatrics Blood and Marrow Transplant

verneris@umn.edu

612-626-2961

Study Officials

• Michael Verneris, M.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• 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: November 1, 2011
• First Posted: November 3, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 28, 2017
• Results First Posted: May 15, 2015

Record last verified: 2017-12

Locations

US (1)