CNDO-109-AANK for AML in First Complete Remission (CR1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Coronado Biosciences, Inc.
Sponsor:
Information provided by (Responsible Party):
Coronado Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT01520558
First received: January 24, 2012
Last updated: March 26, 2013
Last verified: December 2012
  Purpose

This is a multi-center, open-label, non-controlled, non-randomized dose-escalating Phase 1 clinical study designed to examine the safety of infusing escalating doses of CNDO-109-Activated Allogeneic Natural Killer Cells-(from a first or second degree relative), after a preparatory chemotherapy regimen, in adult patients with acute myeloid leukemia (AML) who are in their first complete remission at the time of enrollment, are not candidates for stem cell transplant, and are considered to be at high risk for recurrence.


Condition Intervention Phase
Acute Myeloid Leukemia
Biological: CNDO-109-AANK Cells
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of CNDO-109-Activated Allogeneic Natural Killer Cells in Patients With High Risk Acute Myeloid Leukemia in First Complete Remission (CR1)

Resource links provided by NLM:


Further study details as provided by Coronado Biosciences, Inc.:

Primary Outcome Measures:
  • Define MTD [ Time Frame: up to 30 days post dose ] [ Designated as safety issue: Yes ]
    The primary objective is to define the maximum tolerated dose (MTD), or the maximum tested dose where multiple dose-limiting toxicities (DLTs) are not observed, of CNDO-109-Activated Allogeneic Natural Killer Cells infused after preparative chemotherapy, administered to patients with acute myeloid leukemia (AML) who are in their first complete remission (CR1) at the time of enrollment and are considered to be at high risk for recurrence.


Secondary Outcome Measures:
  • Additional safety profile beyond MTD [ Time Frame: up to 360 days post dose ] [ Designated as safety issue: Yes ]
    Characterize the safety profile of CNDO-109-Activated Allogeneic Natural Killer Cells infusion after preparative therapy by measurement of adverse events, safety labs, vital signs, bone marrow biopsy/aspiration and physical examination.

  • Efficacy [ Time Frame: from the date of documented CR until the first documented progression date or until day 360 post dose whichever is sooner ] [ Designated as safety issue: Yes ]
    Determine relapse free survival (RFS) and overall survival (OS) following infusion with CNDO-109-Activated Allogeneic Natural Killer Cells.


Estimated Enrollment: 33
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CNDO-109-AANK Cells Dose 1
In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the lowest of these three doses (dose 1) is 3×10^5 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.
Biological: CNDO-109-AANK Cells
Single dose, infusion
Other Name: CNDO-109-Activated Allogeneic Natural Killer Cells
Experimental: CNDO-109-AANK Cells Dose 2
In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the middle dose of these three doses (dose 2) is 1×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.
Biological: CNDO-109-AANK Cells
Single dose, infusion
Other Name: CNDO-109-Activated Allogeneic Natural Killer Cells
Experimental: CNDO-109-AANK Cells Dose 3
In stage 1, patients will receive one of three doses of CNDO-109-AANK cells, and the highest dose of these three doses (dose 3) is 3×10^6 cells/kg recipient body weight. In stage 2, the MTD will have been determined and all patients will receive either Dose 1, Dose 2 or Dose 3.
Biological: CNDO-109-AANK Cells
Single dose, infusion
Other Name: CNDO-109-Activated Allogeneic Natural Killer Cells

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The patient has pathologically documented AML and is in CR1 at the time of the screening visit
  2. The patient achieved CR1 within 10 weeks of the screening visit; the patient may have received post-remission consolidation therapy (except for transplant) prior to the screening visit
  3. A bone marrow aspiration performed within 21 days prior to the start of pre-infusion preparative therapy confirms the patient is in CR1
  4. The patient has either refused or is not considered an appropriate immediate candidate for transplantation and is considered to be at high risk for recurrence by having at least one of the following prognostic factors:

    • High risk cytogenetics (-5, -7, del(5q), abnormal 3q, 11q23 translocations, complex cytogenetics) or if cytogenetics are normal the presence of a FLT3 mutation without a NPM1 mutation
    • Age > 60 years
    • Antecedent hematological disorder (AHD)
    • AML that is considered to be therapy-related
    • FAB subtype M0 (minimally differentiated acute myeloblastic leukemia), M6 (acute erythroid leukemias, including erythroleukemia (M6a) and pure erythroid leukemia (M6b)), or M7 (acute megakaryoblastic leukemia)
  5. The patient is male or female, age 18 years or older
  6. The patient has an ECOG performance status of 0, 1, or 2
  7. The patient has an available NK cell donor who is a HLA haploidentical first-degree (parent, child, or sibling) or second-degree (child of a sibling) relative; minimum testing will be for HLA-A, HLA-B, and HLA-DR with donors matched for 3/6, 4/6 or 5/6 antigens
  8. The patient has an absence of coexisting medical problems that would significantly increase the risk of the chemotherapy procedure (e.g. poor left ventricular ejection fraction [LVEF<40%])
  9. The patient has recovered from reversible toxicity from prior therapy. Permanent and stable side effects or changes are acceptable if ≤ Grade 1 (CTCAE, v4.03)
  10. The patient has serum creatinine <2×ULN and not rising for at least 2-4 weeks before chemotherapy. If elevated, the 24-hour creatinine clearance must be >50 mL/min
  11. The patient has serum total bilirubin < 2 g/dL (unless the patient has a diagnosis of Gilbert's disease), SGOT (ALT) <3.5×ULN, and SGPT (AST) <3.5×ULN
  12. The patient has an absolute neutrophil count (ANC) ≥1000/µL, platelets ≥100,000/µL and is not transfusion dependent for platelets and/or red cells
  13. The patient has LVEF ≥40% by ECHO or MUGA scan and no clinically significant abnormalities in 12-lead ECG
  14. The patient has a PT (or INR) and PTT up to 1.25×ULN
  15. The patient must not be dependent on supplemental oxygen
  16. The patient is using an effective contraceptive (per the institutional standard), if procreative potential exists
  17. The patient must be willing and able to comply with all study protocol requirements. The patient or a legally authorized representative must fully understand all elements of the informed consent and have signed the informed consent according to institutional and federal regulatory requirements
  18. The patient has not received an investigational chemotherapy within the last 28 days prior to the screening visit and has never received investigational immunotherapy. In addition, the patient must not receive treatment for AML (including treatment with IL-2 or IFNγ) in the interval of time between the screening visit and initiation of pre-infusion preparative therapy

Exclusion Criteria:

  1. The patient had a previous bone marrow or stem cell transplant
  2. The patient is seropositive for HIV 1, HIV 2, HBV, or HCV
  3. The patient has a psychiatric, addictive, neurological or other disorder that compromises the ability to give informed consent or comply with study requirements
  4. The patient is pregnant (confirmed by urine or serum pregnancy test) or lactating
  5. The patient has a recently diagnosed active malignancy requiring therapy
  6. The patient has an uncontrolled infection, or is receiving anti-fungal treatment for an ongoing infection
  7. The patient has known hypersensitivity to bovine proteins
  8. The patient has any condition that will place the patient at undue risk or discomfort as a result of adherence to study procedures
  9. The patient requires treatment with corticosteroids at a dose > 0.1 mg/kg/day or has a known allergy to DSMO
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01520558

Contacts
Contact: Nova Silver, RN nsilver@coronadobio.com

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Kim Blanton    813-745-3065      
Principal Investigator: Javier Pinilla, MD         
United States, Minnesota
University of Minnesota - Masonic Cancer Center Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Dixie Lewis    612-624-4601      
Principal Investigator: Sarah Cooley, MD         
United States, Missouri
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Ryan Monahan    314-454-8377      
Principal Investigator: Todd Fehniger, MD         
United States, South Carolina
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Jessica Simons    843-792-8856      
Principal Investigator: Robert Stuart, MD         
Sponsors and Collaborators
Coronado Biosciences, Inc.
  More Information

No publications provided

Responsible Party: Coronado Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT01520558     History of Changes
Other Study ID Numbers: CNDO109-001
Study First Received: January 24, 2012
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Coronado Biosciences, Inc.:
Acute Myeloid Leukemia
High Risk Relapse
Complete Remission
Allogeneic Natural Killer Cells

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on August 26, 2014