UARK 2010-35, A Study of Expanded Natural Killer Cell Therapy for Multiple Myeloma (NK2010-35)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT01313897
First received: December 1, 2010
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine the therapeutic efficacy of the exp-NK cell therapy in research participants with relapsed high risk MM [defined as gene expression profile (GEP) 70 gene score ≥0.66 and/or metaphase chromosomal abnormalities and/or high LDH ≥ 360U/L] by establishing the (near) complete response rate. Response rate will be compared to case matched historical controls (patients who relapsed on Total Therapy 2 or 3 with high-risk MM defined as above). Disease-free survival and overall survival will be captured but are not primary or secondary endpoints.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: UARK 2010-35, A Phase II Study of Expanded Natural Killer Cell Therapy for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Arkansas:

Primary Outcome Measures:
  • To determine the therapeutic efficacy of exp-NKcell therapy in research participants [ Time Frame: 2.5 Years ] [ Designated as safety issue: Yes ]
    Response rate will be compared to case matched historical controls (patients who relapsed on Total Therapy 2 or 3 with high-risk MM defined as above). Disease-free survival and overall survival will be captured but are not primary or secondary endpoints.


Secondary Outcome Measures:
  • The number of patients with adverse events, i.e. treatment related deaths, as a measure of safety. [ Time Frame: 3, 6, 9, 12 and 15 months ] [ Designated as safety issue: Yes ]
    If one treatment-related death occurs 3 patients will be enrolled. The trial will be halted if >2 treatment-related deaths occur in the first 6 patients. The trial will be halted if >3 treatment-related deaths occur in the first 9 patients. The trial will be halted if >4 treatment-related deaths occur in the first 12 patients. If ≤4 treatment related-deaths occur in the first 12 patients than a further 3 patients will be enrolled completing the enrollment of the first 15 patients.


Estimated Enrollment: 30
Study Start Date: January 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Velcade for Anti-MM therapy
Day(s) -9,-6,-2 3 doses of Bortezomib at 1.0 mg/m2, i.v.
Drug: Bortezomib
bortezomib to be given days -9, -6, and -2 at 1.0mg/m2, i.v.
Other Names:
  • Bortezomib
  • Velcade

Detailed Description:

The use of auto-exp-NK cells in this protocol makes therapy available to all refractory high risk MM patients, 2/3 of whom would otherwise not have a suitable haploidentical donor. We have shown that NK cells can be expanded both from newly diagnosed high risk MM patients and from refractory, previously heavily treated patients, the very individuals in need of novel therapies such as exp-NK cell infusions. Furthermore, we observed that exp-NK cells have the ability to kill auto-MM cells in vitro compared to no killing with resting auto-NK cells. This may be due to the elevated activation state of exp-NK cells, which allows them to overcome otherwise dominant inhibitory signaling. The incorporation of the proteasome inhibitor bortezomib, which down regulates the principal NK cell inhibitory ligands on MM cells should further increase the efficacy of auto-exp-NK cells. Because there is no risk for GvHD, CD3+ T cell depletion will not be necessary for auto-exp-NK cell products.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patient (Recipient of NK Cells) Inclusion Criteria
  • Relapsed patients must have high risk disease as defined by GEP risk score of ≥ 0.66 or metaphase cytogenetic abnormalities or LDH ≥ 360 U/L (Rule out hemolysis, infection and contact PI for clarification if any doubt) Patients must have had at least 1 line of prior chemotherapy and/or have relapsed after auto- PBSCT.
  • For subjects who have had a prior transplant, ≥2 months must have relapsed after the last transplant prior to enrollment.
  • Zubrod ≤ 2, unless solely due to symptoms of MM-related (bone) disease.
  • Patients must have a platelet count of ≥ 50,000/µL within 35 days of registration, unless lower levels are explained by extensive bone marrow plasmacytosis or extensive prior therapy.
  • Patients must be at least 18 years of age and not older than 75 years of age at the time of registration.
  • Participants must have preserved renal function as defined by a serum creatinine level of ≤ 3 mg/dL within 35 days of registration.
  • Participants must have an ejection fraction by ECHO or MUGA scan ≥ 40% within 90 days prior to registration.
  • Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted within 90 days prior to registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, exception may be granted if the principal investigator documents that the patient is a candidate for high dose therapy.
  • Patients must have signed an IRB-approved informed consent and HIPAA authorization form.
  • Either a haploidentical family donor fit to undergo leukapheresis is available or the recipient is fit to undergo leukapheresis for exp-NK cell generation (see donor selection).
  • Patient (Recipient of NK Cells) Exclusion criteria
  • History of poorly controlled hypertension, diabetes mellitus, or any other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or could be considered to be an exclusion criterion deemed by the PI.
  • Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds three years as determined by the PI.
  • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  • Donor Inclusion Criteria
  • The source of the NK cells will be either A) a family member who is HLA haploidentical to the recipient, or B) if a suitable haploidentical donor is not available, the recipient may be the source of the NK cells.
  • HLA typing will be performed by the Arkansas Children's Hospital clinical laboratory.
  • If the recipient expresses HLA-C group I, HLA-C group II, and Bw4 KIR ligands, then a KIR-ligand mismatched haploidentical donor cannot be found, and the recipient will be the source of the NK cells.
  • If the recipient fails to express one or more of the primary KIR ligands (HLA-C group I, HLA-C group II, and Bw4) then family member donors will be HLA typed in an effort to find a haploidentical donor. If multiple haploidentical donors are available, KIR phenotyping will be performed in Dr. van Rhee's research laboratory to select a KIR mismatched donor whenever possible.
  • Donor selection will be performed by the PI or one of the MD co-investigators if Dr. van Rhee is not available.
  • Signed IRB approved consent and HIPAA authorization form.
  • Donor is not HIV I/II (+).
  • Donor is not HTLV-I/II (+).
  • Donor is not Hepatitis B or C (+) unless positive due to previous vaccination or has received therapy and is negative for Hepatitis B or C by RT-PCR.
  • Donor is a suitable candidate for insertion of apheresis catheter. Donors with unusual anatomy or vascular anomalies preventing insertion of a pheresis catheter will be rejected.
  • Age 18 years or greater or has signed an Assent and be age ≥16 years.
  • Donor has a negative pregnancy test by serum or urine test.
  • In preparation for the peripheral blood mononuclear cell donation, the donor will undergo a detailed medical history and physical examination. Clinical studies will include blood chemistries (electrolytes, liver function and CRP) CBC with differential and platelets, PT/PTT, viral panel, EKG (age over 40 yrs), and chest x-ray (age over 40yrs). Fitness to donate cells for NK expansion will be evaluated by a physician not involved in the initial assessment of the exp-NK cell recipient for enrollment onto the protocol.
  • Serologic evaluation will be used to assess exposure to syphilis, West Nile Virus, Chagas, CMV IgG, hepatitis B, and C, HIV I and II, and HTLV I/II. An HIV-I/II[+] and HTLV-1/II (+) donor will be rejected on medical grounds. Donors who been vaccinated against hepatitis B and who have antibodies against hepatitis B surface antigen are allowed.
  • Haplo-identical donor must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to donation.

Exclusion Criteria:

  • Patient (Recipient of NK Cells) Exclusion criteria
  • History of poorly controlled hypertension, diabetes mellitus, or any other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or could be considered to be an exclusion criterion deemed by the PI.
  • Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds three years as determined by the PI.
  • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01313897

Locations
United States, Arkansas
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
Sponsors and Collaborators
University of Arkansas
Investigators
Principal Investigator: Frits van Rhee, M.D., PHD. University of Arkansas
  More Information

No publications provided

Responsible Party: University of Arkansas
ClinicalTrials.gov Identifier: NCT01313897     History of Changes
Other Study ID Numbers: 2010-35, IND 14560
Study First Received: December 1, 2010
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arkansas:
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014