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

NCT00941928 | Terminated Phase 2 Results

• 1 other identifier: 2007-0160
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Leukemia; Pediatric Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP)

  TTP calculated as average time, in months, from baseline to participants disease progression or death, monitored for a minimum of 1 year

  1 Year

Secondary Outcomes (1)

• Overall Survival (OS)

  Minimum of 1 year, or until disease progression or death

Study Arms (1)

Haploidentical NK cells + Epratuzumab

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mesna; Procedure: Infusion of NK cells; Drug: Interleukin-2

Interventions

Epratuzumab DRUG

360 mg/m\^2 once a day by vein on Day -4, Day -1 and Days 3, 6, 10, 13 and 17.

Haploidentical NK cells + Epratuzumab

Fludarabine DRUG

25 mg/m\^2 once a day by vein on Day -6 through Day -2 over 30 minutes.

Also known as: Fludara, Fludarabine Phosphate

Haploidentical NK cells + Epratuzumab

Cyclophosphamide DRUG

60 mg/kg once a day by vein on Days -5 and -4 over 2 hours.

Also known as: Cytoxan, Neosar

Haploidentical NK cells + Epratuzumab

Mesna DRUG

12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.

Also known as: Mesnex

Haploidentical NK cells + Epratuzumab

Infusion of NK cells PROCEDURE

Transplant of Haploidentical NK cells by vein on Day 0.

Also known as: Stem Cell Transplant, Natural Killer Cells

Haploidentical NK cells + Epratuzumab

Interleukin-2 DRUG

Subcutaneous injections three times a week for 9 doses on Days 0 to 21.

Also known as: IL-2, Proleukin

Haploidentical NK cells + Epratuzumab

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of CD22+ acute lymphoblastic leukemia that is a. refractory to therapy or b. in second or greater relapse without other standard therapeutic options
• 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)
• Off prednisone or other immunosuppressive medications for at least 3 days prior to both the lymphodepleting regimen and the NK infusion
• Zubrod performance scale \</= 2 or Lansky performance scale \>/= 60
• 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
• 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)
• Pulmonary symptoms controlled by medication and pulse oximetry \>/= 92% room air
• 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
• Requirement of sexually active females and males to use any form of contraception considered effective and medically acceptable by the Investigator. \[Acceptable forms: birth control implants, birth control pills, a vasectomy (male surgical sterilization), or a double-barrier method (any 2 of the following in combination: intrauterine device (IUD), male or female condom with spermicidal gel, a diaphragm, a sponge, and/or cervical cap)\]
• Negative serology for human immunodeficiency virus (HIV)
• 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
• 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
• 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
• Donor must meet standard medical eligibility criteria for allogeneic stem cell donation

You may not qualify if:

• Active central nervous system (CNS) leukemia
• Active infection (defined as on antimicrobial therapy and or febrile)
• Breast-feeding females
• Currently using a ventilator or requiring supplemental oxygen
• Currently undergoing dialysis
• Currently using a Phase I, II, or III investigational agent. These agents should be stopped within 21 days of NK infusion
• New detected cardiac arrhythmia not controlled with medical management within prior 72 hour period.
• Hypotension requiring pressor support within prior 72 hour period
• 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
• Taking corticosteroids by mouth or intravenously within prior 72 hour period
• 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.)
• Seizure activity or clinically detectable encephalopathy or new focal neurologic deficits within prior 72 hour period
• Donor has active infection (defined as on antimicrobial therapy and/or febrile) within 7 days of apheresis
• Donor is pregnant female or breast-feeding female (within 7 days of apheresis)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Leukemia; Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

epratuzumab; fludarabine; fludarabine phosphate; Cyclophosphamide; Mesna; Stem Cell Transplantation; IL32 protein, human; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; 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: Anna Franklin, MD, Assistant Professor
• Organization: University of Texas MD Anderson Cancer Center

rnjackso@mdanderson.org

713-792-3497

Study Officials

• Anna Franklin, MD

  UT MD Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: July 16, 2009
• First Posted: July 20, 2009
• Study Start: July 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 22, 2014
• Results First Posted: August 28, 2013

Record last verified: 2014-05

Locations

US (1)