Trial Title:
A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions As Adoptive Immunotherapy in Combination with Gemcitabine and Docetaxel in Patients with Relapsed or Refractory Pediatric Bone and Soft Tissue
NCT ID:
NCT05634369
Condition:
Pediatric Sarcoma, Refractory
Pediatric Sarcoma, Relapsed
Conditions: Official terms:
Sarcoma
Dexamethasone
Gemcitabine
Docetaxel
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single arm, unblinded, phase I/II study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
GEM/DOX + TGFBi expanded NK cells
Description:
8 cycles consisting of gemcitabine, docetaxel, supportive dexamethasone and
pegfilagrastim, and universal donor, TGFBi ex vivo expanded NK cells
- Each cycle will be repeated every 21 days based upon disease response and toxicity
criteria
- Tumor response assessed after Cycles 2, 4, 6, and 8
1. Gemcitabine 675mg/m2/dose IV on Days 1 and 8
2. Docetaxel 75mg/m2/dose IV on Day 8
3. Dexamethasone 3mg/m2/dose (max 8 mg/dose) PO BID on Days 7, 8, and 9
4. Pegfilgrastim (Peg-GCSF) 0.1mg/kg/dose (max 6 mg/dose) SQ on Day 9
5. NK cells 1 x 10e8 cells/kg/dose IV on Day 12 (+ 1-2 days)
Arm group label:
Treatment
Other name:
Docetaxel
Other name:
Dexamethasone
Other name:
Pegfilgrastim
Other name:
Gemcitabine
Summary:
The purpose of this study is to determine if the addition of infusions of a type of
immune cell called a "natural killer", or NK cell to the sarcoma chemotherapy regimen
GEM/DOX (gemcitabine and docetaxel) can improve outcomes in people with childhood
sarcomas that have relapsed or not responded to prior therapies.
The goals of this study are:
- To determine the safety and efficacy of the addition of adoptive transfer of
universal donor, TGFβ imprinted (TGFβi), expanded NK cells to the pediatric sarcoma
salvage chemotherapeutic regimen gemcitabine/docetaxel (GEM/DOX) for treatment of
relapsed and refractory pediatric sarcomas To determine the 6-month progression free
survival achieved with this treatment in patients within cohorts of relapsed or
refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and non-rhabdomyosarcoma
soft tissue sarcoma.
- To identify toxicities related to treatment with GEM/DOX + TGFβi expanded NK cells
Participants will receive study drugs that include chemotherapy and NK cells in cycles;
each cycle is 21 days long and you can receive up to 8 cycles.
- Gemcitabine (GEM): via IV on Days 1 and 8
- Docetaxel (DOX): via IV on Day 8
- Prophylactic dexamethasone: Day 7-9 to prevent fluid retention and hypersensitivity
reaction
- Peg-filgrastim (PEG-GCSF) or biosimilar: Day 9 to help your white blood cell recover
and allow more chemotherapy to be given
- TGFβi NK cells: via IV on Day 12
Detailed description:
This is a multi-center study with rolling safety and toxicity analysis, to determine the
safety and efficacy of the addition of adoptive transfer of universal donor, TGFβ
imprinted (TGFβi), expanded NK cells to the pediatric sarcoma salvage chemotherapeutic
regimen gemcitabine/docetaxel (GEM/DOX) for treatment of relapsed and refractory
pediatric sarcomas, identify toxicities related to treatment with GEM/DOX + TGFβi
expanded NK cells, and assess in vivo persistence of expanded, universal donor, TGFβi NK
cells after adoptive transfer and correlate with clinical outcomes.
The planned therapy will involve 8 cycles of 21 days each consisting of gemcitabine,
docetaxel, supportive dexamethasone and peg-filgrastim, and universal donor, TGFβi ex
vivo expanded NK cells (Cycles 1-6).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must be between the ages > 12 years and ≤ 40 years of age and have had a
relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma or
non-rhabdomyosarcoma soft tissue sarcoma.
2. Patients must have measurable disease using RECIST 1.1 criteria
3. Patients must have had at least one and no more than four total lines of systemic
treatment for relapse sarcoma. Local control with surgical resection or radiation
therapy of the primary tumor and any metastatic sites as clinically indicated as
standard of care per the treating physician must be considered prior to enrollment.
4. Prior Therapy: Therapy may not have been received more recently than the timeframes
defined below:
- Myelosuppressive chemotherapy: Patients must not have received myelosuppressive
therapy within 14 days of protocol therapy
- Radiation: At least 2 weeks must have elapsed from the start of protocol
therapy since local palliative XRT (small port); 4 weeks must have elapsed for
all other radiation therapy
- Hematopoietic Cell Transplant (HCT): Patients must have at least 6 weeks
elapsed after autologous and allogeneic hematopoietic cell transplant
- Biologic (anti-neoplastic agent): At least 7 days or 5 half-lives of the drug,
whichever is longer, must have elapsed from the start of protocol therapy since
the completion of therapy with a biologic agent.
- Monoclonal antibodies: At least 3 weeks must have elapsed from the start of
protocol therapy since prior therapy that included a monoclonal antibody.
- Prior use of Gemcitabine and/or Docetaxel: Patients who have received these
agents for prior treatment may be included if previous treatments were given ≥
6 months prior to enrollment on this study, and there were no allergic
reactions, pulmonary edema or fibrosis, Grade 3 or higher neuropathy or other
non-hematologic Grade 4 adverse events related to gemcitabine and/or docetaxel
therapies.
4) Performance status: Karnofsky ≥ 60 for patients ≥16 years of age. Lansky score of ≥
60 for patients < 16 years of age (see Appendix A) 5) Organ Function Requirements:
Patients must have normal organ and marrow function within 7 days of starting
protocol therapy as defined below:
- Absolute Neutrophil Count ≥1000/mcL
- Platelet count ≥100,000/mcL independent of transfusion
- Total bilirubin < 1.5x upper limit of normal for age
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x institutional upper limit of normal
- Serum creatinine < 1.5 x upper limit of normal based on age/gender (Table 3) OR
creatinine clearance ≥70 mL/min/1.73 m2 for patients with creatinine levels above
institutional normal
- Shortening fraction ≥ 27% by ECHO OR ejection fraction of ≥ 50% by ECHO or gated
radionuclide study
- Echocardiogram done within 12 months of study entry will be acceptable. If
patient has required anthracycline chemotherapy since last ECHO and enrollment
on this study, echocardiogram should be repeated.
- No evidence for dyspnea at rest, no chronic oxygen requirement, and room air pulse
oximetry >94% if there is a clinical indication for pulse oximetry 6) Neuropathy:
Patients must have ≤ Grade 2 neuropathy at enrollment 7) Patients with seizure
disorders may be enrolled if seizures are well controlled on anti-convulsant, with
the exception of diazepam given its potential deleterious effects on NK cell
activity.
8) Contraception: The effects of expanded NK cells on the developing human fetus
are unknown. For this reason and because the chemotherapeutic preparative
agents as well as other therapeutic agents used in this trial are known to be
teratogenic, women of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior
to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician
immediately. Men treated or enrolled on this protocol must also agree to use
adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of preparatory regimen
administration.
9) All patients and/or their parents or legal guardians must have the ability to
understand and the willingness to sign a written informed consent/assent
document.
Exclusion Criteria:
1. Patients who are receiving any other investigational agents.
2. Patients must not be receiving any additional medicines being given for the specific
purpose of treating cancer
3. Patients with a history of allergic reactions attributed to docetaxel, gemcitabine,
or peg-filgrastim or biosimilar
4. Patients who have received any prior cellular therapies, such as CAR-T cells or
other expanded or manufactured cellular products.
5. Patients with bone marrow only disease are not eligible for this study.
6. Patients who, in the judgment of the treating physician, has tumors near critical
structures for which transient swelling would cause substantial symptoms, such as
tumor within the bowel mucosa
7. Patients with CNS metastatic disease will not be eligible for this study.
8. Concomitant Medications:
- Due to their effect on NK cell function, systemic corticosteroids outside of
the supportive dexamethasone given from day 7 through 9 should be used ONLY for
life-threatening conditions (i.e., life-threatening allergic reactions and
anaphylaxis such as bronchospasm, stridor) unresponsive to other measures. The
use of dexamethasone as an anti-emetic is not permitted. Corticosteroid therapy
can be used as a premedication for transfusion in patients known to have a
history of transfusion reactions or for treatment of an unexpected transfusion
reaction (hydrocortisone 2 mg/kg or less or an equivalent dose of an
alternative corticosteroids). The use of steroids during protocol therapy other
than the study- required prophylactic dexamethasone doses requires clear
justification and documentation of use for a life-threatening condition.
- The following are also prohibited while on study treatment
- Strong CYP3A4 inducers. Because the lists of these agents are constantly
changing, it is important to regularly consult a frequently-updated list
such as http://medicine.iupui.edu/clinpharm/ddis/; medical reference texts
such as the Physicians' Desk Reference may also provide this information.
- Diazepam
- Chemotherapeutic agents other than the study drugs
9. Uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection
- psychiatric illness/social situations that would limit compliance with study
requirements
10. Pregnancy or Breast-Feeding: Pregnant or breast-feeding woman will not be entered on
this study due to risks of fetal and teratogenic adverse events as seen in
animal/human studies with Gemcitabine and Docetaxel
11. HIV Infection: HIV-positive patients on combination antiretroviral therapy are
ineligible because of the potential for pharmacokinetic interactions with the study
medications. In addition, these patients are at increased risk of lethal infections
when treated with marrow-suppressive therapy. Appropriate studies will be undertaken
in patients receiving combination antiretroviral therapy when indicated
12. Patients who in the opinion of the investigator may not be able to comply with the
safety monitoring requirements of the study are not eligible.
Gender:
All
Minimum age:
12 Years
Maximum age:
40 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama
Address:
City:
South Birmingham
Zip:
35233
Country:
United States
Status:
Recruiting
Contact:
Last name:
Elizabeth Alva, MD
Phone:
205-683-9285
Email:
ealva@peds.uab.edu
Contact backup:
Last name:
Elizabeth Alva, MD
Facility:
Name:
Children's Hospital of Los Angeles
Address:
City:
Los Angeles
Zip:
90027
Country:
United States
Status:
Recruiting
Contact:
Last name:
Fariba Navid, MD
Phone:
323-361-2121
Email:
fnavid@chla.usc.edu
Contact backup:
Last name:
Fariba Navid, MD
Facility:
Name:
University of Florida
Address:
City:
Gainesville
Zip:
32610
Country:
United States
Status:
Recruiting
Contact:
Last name:
John Ligon, MD
Phone:
352-273-9120
Email:
john.ligon@ufl.edu
Contact backup:
Last name:
John Ligon, MD
Facility:
Name:
Nemours Jacksonville
Address:
City:
Jacksonville
Zip:
32207
Country:
United States
Status:
Recruiting
Contact:
Last name:
Anderson Collier, III, MD
Phone:
904-697-3793
Email:
Anderson.Collier@nemours.org
Contact backup:
Last name:
Anderson Collier, III, MD
Facility:
Name:
University of Miami
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Aditi Dhir, MD
Phone:
305-243-4830
Email:
aditi.dhir@med.miami.edu
Contact backup:
Last name:
Aditi Dhir, MD
Facility:
Name:
Johns Hopkins All Children's Hospital
Address:
City:
Saint Petersburg
Zip:
33701
Country:
United States
Status:
Recruiting
Contact:
Last name:
Natalie Booth, DO
Phone:
727-767-3513
Email:
nbooth3@jh.edu
Contact backup:
Last name:
Natalie Booth, DO
Facility:
Name:
Washington University/St Louis Childrens
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Amy Armstrong, MD
Phone:
314-454-6018
Email:
armstrongae@wustl.edu
Contact backup:
Last name:
Amy Armstrong, MD
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alice Lee, MD
Phone:
718-741-2342
Email:
alee5@montefiore.org
Contact backup:
Last name:
Alice Lee, MD
Facility:
Name:
Roswell Park Comprehensive Cancer Center
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ajay Gupta, MD
Phone:
716-845-2333
Email:
Ajay.Gupta@RoswellPark.org
Contact backup:
Last name:
Ajay Gupta, MD
Facility:
Name:
Levine Cancer Institute
Address:
City:
Charlotte
Zip:
28203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Erin M Trovillion, MD
Phone:
704-381-9900
Email:
Erin.Trovillion@atriumhealth.org
Contact backup:
Last name:
Erin M Trovillion, MD
Facility:
Name:
Duke Children's Hospital/Duke Health
Address:
City:
Durham
Zip:
27710
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jessica Sun, MD
Phone:
919-668-1102
Email:
jessica.sun@duke.edu
Contact backup:
Last name:
Jessica Sun, MD
Facility:
Name:
Nationwide Children's Hospital
Address:
City:
Columbus
Zip:
43205
Country:
United States
Status:
Recruiting
Contact:
Last name:
Clelie Peck
Phone:
6147225634
Email:
clelie.peck@nationwidechildrens.org
Contact backup:
Last name:
Bhuvana Setty, MD
Facility:
Name:
UT Southwestern
Address:
City:
Dallas
Zip:
75390
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Campbell, MD
Phone:
214-456-2382
Email:
Matthew.Campbell@UTSouthwestern.edu
Contact backup:
Last name:
Matthew Campbell, MD
Facility:
Name:
University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Dristhi Ragoonanan, MD
Phone:
713-792-6620
Email:
DRagoonanan@mdanderson.org
Contact backup:
Last name:
Jonathan Gill, MD
Phone:
713-745-3145
Email:
jbgill@mdanderson.org
Contact backup:
Last name:
Jonathan Gill, MD
Contact backup:
Last name:
Dristhi Ragoonanan, MD
Facility:
Name:
Primary Children's Hospital
Address:
City:
Salt Lake City
Zip:
84113
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Dietz, DO
Phone:
801-662-4700
Email:
matthew.dietz@hsc.utah.edu
Contact backup:
Last name:
Matthew Dietz, DO
Start date:
November 14, 2022
Completion date:
December 2027
Lead sponsor:
Agency:
Nationwide Children's Hospital
Agency class:
Other
Collaborator:
Agency:
National Pediatric Cancer Foundation
Agency class:
Other
Source:
Nationwide Children's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05634369
