Haploidentical Natural Killer (NK) Cells With Epratuzumab for Relapsed Acute Lymphoblastic Leukemia (ALL)

This study has been terminated.
(Slow accrual)
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00941928
First received: July 16, 2009
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to learn if transferring the donor's NK cells, in combination with an antibody called epratuzumab and low-dose interleukin (IL-2), into your body can be done safely. Researchers want to find out if the infused NK cells will survive after the infusion and if the NK cell infusion helps to destroy cancer cells in the recipient's body and possibly to help control the disease.

Primary Objectives:

· Evaluate the feasibility of collecting an adequate number of natural killer (NK) cells from a donor and evaluate the safety of a haploidentical donor-derived NK cell infusion, Epratuzumab, and low-dose interleukin-2 (IL-2).

Secondary Objectives:

  • Quantification and persistence of the infused donor NK cell in vivo;
  • Quantification and persistence of cytokine levels;
  • Assessment of NK cell immunophenotype and function;
  • Correlate above with anti-tumor effect.

Condition Intervention Phase
Leukemia
Pediatric Cancer
Drug: Epratuzumab
Drug: Fludarabine
Drug: Cyclophosphamide
Drug: Mesna
Procedure: Infusion of NK cells
Drug: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Adoptive Transfer of Haploidentical NK Cells in Combination With Epratuzumab for the Treatment of Relapsed Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Time to Progression (TTP) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    TTP calculated as average time, in months, from baseline to participants disease progression or death, monitored for a minimum of 1 year


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Minimum of 1 year, or until disease progression or death ] [ Designated as safety issue: No ]
    Number of surviving participants without disease progression or death for any reason at one year post treatment.


Enrollment: 2
Study Start Date: July 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
Drug: Epratuzumab
360 mg/m^2 once a day by vein on Day -4, Day -1 and Days 3, 6, 10, 13 and 17.
Drug: Fludarabine
25 mg/m^2 once a day by vein on Day -6 through Day -2 over 30 minutes.
Other Names:
  • Fludara
  • Fludarabine Phosphate
Drug: Cyclophosphamide
60 mg/kg once a day by vein on Days -5 and -4 over 2 hours.
Other Names:
  • Cytoxan
  • Neosar
Drug: Mesna
12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
Other Name: Mesnex
Procedure: Infusion of NK cells
Transplant of Haploidentical NK cells by vein on Day 0.
Other Names:
  • Stem Cell Transplant
  • Natural Killer Cells
Drug: Interleukin-2
Subcutaneous injections three times a week for 9 doses on Days 0 to 21.
Other Names:
  • IL-2
  • Proleukin

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Recipient Inclusion criteria (within 28 days of this protocol's lymphodepleting conditioning regimen and after donor and recipient consent-signing)
  2. Diagnosis of CD22+ acute lymphoblastic leukemia that is a. refractory to therapy or b. in second or greater relapse without other standard therapeutic options
  3. Patient may have been the recipient of an allogeneic hematopoietic stem cell transplant; however; there must be no evidence of Graft-versus-host disease (GVHD)
  4. Off prednisone or other immunosuppressive medications for at least 3 days prior to both the lymphodepleting regimen and the NK infusion
  5. Zubrod performance scale </= 2 or Lansky performance scale >/= 60
  6. Adequate renal function defined as: Serum creatinine (Cr), for adults </= 2 mg/dL, for children </= 2 mg/dL or </= 2 times upper limit of normal (ULN) for age (whichever is less). If abnormal renal function, then Cr clearance >/= 60 mL/min/1.73 m^2
  7. Adequate liver function defined as: Total bilirubin </= 2 mg/dL and serum glutamic-pyruvic transaminase (SGPT)/ alanine transaminase(ALT) </= 5 * ULN for age (unless Gilbert's disease or abnormal liver function due to primary disease)
  8. Pulmonary symptoms controlled by medication and pulse oximetry >/= 92% room air
  9. Negative serum test to rule out pregnancy within 2 weeks prior to registration in females of childbearing potential (non childbearing is defined as greater than one year post-menopausal or surgically sterilized
  10. Requirement of sexually active females and males to use any form of contraception considered effective and medically acceptable by the Investigator. [Acceptable forms: birth control implants, birth control pills, a vasectomy (male surgical sterilization), or a double-barrier method (any 2 of the following in combination: intrauterine device (IUD), male or female condom with spermicidal gel, a diaphragm, a sponge, and/or cervical cap)]
  11. Negative serology for human immunodeficiency virus (HIV)
  12. Donor must be related to recipient and is predicted to be alloreactive based upon the presence of the relevant KIR genes and incompatibility with the recipient for HLA C or Bw antigens
  13. Donor must have infectious disease marker testing [Hepatitis B, C, HIV, CMV, Syphilis (RPR), Chagas, HTLV, and West Nile Virus] and CBC differential and platelet studies that meet standard medical eligibility criteria for allogeneic blood stem cell donation within 7 days of apheresis
  14. Donor, if a female of childbearing potential (non-childbearing is defined as greater than one year post-menopause or surgically sterilized), must have a negative serum test to rule out pregnancy within 14 days of apheresis
  15. Donor must meet standard medical eligibility criteria for allogeneic stem cell donation

Exclusion Criteria:

  1. Exclusion criteria applies to both the initiation of conditioning regimen and to the NK infusion
  2. Active central nervous system (CNS) leukemia
  3. Active infection (defined as on antimicrobial therapy and or febrile)
  4. Breast-feeding females
  5. Currently using a ventilator or requiring supplemental oxygen
  6. Currently undergoing dialysis
  7. Currently using a Phase I, II, or III investigational agent. These agents should be stopped within 21 days of NK infusion
  8. New detected cardiac arrhythmia not controlled with medical management within prior 72 hour period.
  9. Hypotension requiring pressor support within prior 72 hour period
  10. Uncontrolled infection defined as daily fever greater than or equal to 38.2°C within prior 24 hours and new positive culture for bacteria, fungus, or virus within 72 hours prior to NK -cell infusion, if clinically indicated
  11. Taking corticosteroids by mouth or intravenously within prior 72 hour period
  12. Ascites requiring paracentesis within prior 72 hour period. (If the patient requires paracentesis within 72 hours of NK cell infusion, they will not be eligible to receive the infusion.)
  13. Seizure activity or clinically detectable encephalopathy or new focal neurologic deficits within prior 72 hour period
  14. Donor has active infection (defined as on antimicrobial therapy and/or febrile) within 7 days of apheresis
  15. Donor is pregnant female or breast-feeding female (within 7 days of apheresis)
  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: NCT00941928

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: Anna Franklin, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00941928     History of Changes
Other Study ID Numbers: 2007-0160
Study First Received: July 16, 2009
Results First Received: May 22, 2013
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Blood And Marrow Transplantation
Relapsed Acute Lymphoblastic Leukemia
ALL
Leukemia
Pediatrics
Haploidentical NK cells
Cyclophosphamide
Cytoxan
Neosar
Epratuzumab
Fludarabine
Fludarabine Phosphate
Fludara
Interleukin-2
IL-2
Proleukin
Low-dose interleukin
Mesna
Mesnex
Natural Killer Cells
NK Cells Transplant

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mesna
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Analgesics

ClinicalTrials.gov processed this record on July 26, 2014