Research Study Utilizing Expanded Multi-antigen Specific Lymphocytes for the Treatment of Solid Tumors
| Status: | Recruiting |
|---|---|
| Conditions: | Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any - 60 |
| Updated: | 11/24/2018 |
| Start Date: | November 2016 |
| End Date: | April 2020 |
| Contact: | Holly Meany, MD |
| Email: | HMeany@childrensnational.org |
| Phone: | 202-476-2800 |
Patients with high-risk solid tumors, those that are refractory to standard up front therapy
or relapse after completion of therapy, have a very poor prognosis despite attempts to induce
remission with salvage regimen. Novel therapies are critical for this patient population with
high-risk cancer.
The ability of tumors to be recognized and lysed by the immune system offers a unique
opportunity to aid in tumor eradication by expanding and activating these anti-tumor cells.
Through this ability to harness sophisticated and specific immunotherapy, residual or
relapsed disease that is resistant to chemotherapy and/or radiotherapy could be eradicated.
Prior studies have suggested both safety of expanded specific T cells and efficacy in the
setting of melanoma, lymphoma or viral eradication. While this therapy has previously been
limited by the versatility of the tumor to down-regulate antigens and evade a single
immune-target, the use of multi-antigen specific T cells may permit better and more durable
anti-tumor immunity. Thus, the investigators propose to infuse these specific multi-antigen
anti-tumor T lymphocytes into patients with high risk solid tumors. This trial will be
conducted to demonstrate safety of these cells and generate efficacy and biology data that
may be important for future studies that may enhance tumor immunotherapy.
or relapse after completion of therapy, have a very poor prognosis despite attempts to induce
remission with salvage regimen. Novel therapies are critical for this patient population with
high-risk cancer.
The ability of tumors to be recognized and lysed by the immune system offers a unique
opportunity to aid in tumor eradication by expanding and activating these anti-tumor cells.
Through this ability to harness sophisticated and specific immunotherapy, residual or
relapsed disease that is resistant to chemotherapy and/or radiotherapy could be eradicated.
Prior studies have suggested both safety of expanded specific T cells and efficacy in the
setting of melanoma, lymphoma or viral eradication. While this therapy has previously been
limited by the versatility of the tumor to down-regulate antigens and evade a single
immune-target, the use of multi-antigen specific T cells may permit better and more durable
anti-tumor immunity. Thus, the investigators propose to infuse these specific multi-antigen
anti-tumor T lymphocytes into patients with high risk solid tumors. This trial will be
conducted to demonstrate safety of these cells and generate efficacy and biology data that
may be important for future studies that may enhance tumor immunotherapy.
This protocol is designed as a phase I dose-escalation study. In each treatment group (A and
B), patients will be enrolled to one of the following TAA-CTL dose levels:
Dose Level One: 1 x 107 cells/m2 Dose Level Two: 2 x 107 cells/m2 Dose Level Three: 4 x 107
cells/m2 Two to four patients will be enrolled at each dose level until the maximum tolerated
dose (MTD) is determined at which point to ensure safety a total 8 patients will be treated
at the MTD. Expansion cohorts of Group B patients with Wilms tumor, neuroblastoma,
rhabdomyosarcoma, adenocarcinoma and esophageal cancer will be permitted to enroll up to 6
additional patients in each disease group, to be treated at the MTD. Each patient will
receive at least one TAA-CTL infusion and may receive a maximum of 8 doses total. Dose
escalation will occur once at least 2 patients have completed the 45 day follow up period
following their first TAA-CTL infusion. The first and second doses will be administered 45
days apart then additional doses will be spaced every 28 days. The expected volume of each
infusion is 1 to 10 cc.
Patients will receive cells due to the presence of refractory disease and/or high risk for
disease relapse and/or residual detectable disease following HSCT or conventional therapy at
the time of the infusion. Group A and Group B patients will use the dose escalation strategy
described above. Ideally, patients should not receive other systemic antineoplastic agents
for at least 45 days after the infusion of TAA- CTL (for purposes of evaluation), although
such treatment may be added if deemed critical for patient care by the attending physician.
If patients with measurable or evaluable disease have a response of stable disease or better
by RECIST criteria (see section 3.2.1) at the day 28 evaluation after dose 2 or subsequent
evaluations they are eligible to receive up to 6 additional doses of CTLs at 28 day
intervals. Each subsequent doseis expected to be at the enrollment dose level (i.e. no
subsequent dose escalation). Following dose 1, if a patient's T cell supply is insufficient
for subsequent doses at the enrollment dose level, further treatments may be administered at
a lower dose level at the treating physician's discretion.
B), patients will be enrolled to one of the following TAA-CTL dose levels:
Dose Level One: 1 x 107 cells/m2 Dose Level Two: 2 x 107 cells/m2 Dose Level Three: 4 x 107
cells/m2 Two to four patients will be enrolled at each dose level until the maximum tolerated
dose (MTD) is determined at which point to ensure safety a total 8 patients will be treated
at the MTD. Expansion cohorts of Group B patients with Wilms tumor, neuroblastoma,
rhabdomyosarcoma, adenocarcinoma and esophageal cancer will be permitted to enroll up to 6
additional patients in each disease group, to be treated at the MTD. Each patient will
receive at least one TAA-CTL infusion and may receive a maximum of 8 doses total. Dose
escalation will occur once at least 2 patients have completed the 45 day follow up period
following their first TAA-CTL infusion. The first and second doses will be administered 45
days apart then additional doses will be spaced every 28 days. The expected volume of each
infusion is 1 to 10 cc.
Patients will receive cells due to the presence of refractory disease and/or high risk for
disease relapse and/or residual detectable disease following HSCT or conventional therapy at
the time of the infusion. Group A and Group B patients will use the dose escalation strategy
described above. Ideally, patients should not receive other systemic antineoplastic agents
for at least 45 days after the infusion of TAA- CTL (for purposes of evaluation), although
such treatment may be added if deemed critical for patient care by the attending physician.
If patients with measurable or evaluable disease have a response of stable disease or better
by RECIST criteria (see section 3.2.1) at the day 28 evaluation after dose 2 or subsequent
evaluations they are eligible to receive up to 6 additional doses of CTLs at 28 day
intervals. Each subsequent doseis expected to be at the enrollment dose level (i.e. no
subsequent dose escalation). Following dose 1, if a patient's T cell supply is insufficient
for subsequent doses at the enrollment dose level, further treatments may be administered at
a lower dose level at the treating physician's discretion.
Inclusion Criteria:
Recipient procurement inclusion criteria
- Diagnosis of high-risk solid tumors: Ewing sarcoma, Wilms tumor, neuroblastoma,
rhabdomyosarcoma, soft tissue sarcomas, osteosarcoma, adenocarcinoma and esophageal
carcinoma
- Refractory disease, residual detectable disease following conventional therapy or
relapsed disease
- 6 months to 60 years of age at enrollment
- Karnofsky/Lansky score of ≥ 50%
- ANC greater than 500/µL (may be supported with G-CSF)
- Bilirubin ≤ 2.5 mg/dL
- AST/ALT ≤ 5x the upper limit of normal for age
- Serum creatinine < 1.0 mg/dL or 2 x the upper limit of normal for age (whichever is
higher)
- Pulse oximetry of > 90% on room air
- Agree to use contraceptive measures during study protocol participation (when age
appropriate)
- LVEF > 50% or LVSF > 27 % if history of TBI
- Patient or parent/guardian capable of providing informed consent
Exclusion Criteria:
Recipient Procurement exclusion criteria
- Patients with uncontrolled infections
- Patients with active HIV
- Current evidence of GVHD > grade 2 or chronic GVHD manifestations: bronchiolitis
obliterans syndrome, sclerotic GVHD, or serositis.
- Pregnant or lactating females
- Prior immunotherapy with an investigational agent within the last 28 days prior to
procurement
Recipient Inclusion to administer cells:
- Steroids less than 0.5 mg/kg/day prednisone (or equivalent)
- Karnofsky/Lansky score of ≥ 50%
- Bilirubin ≤ 2.5 mg/dL
- AST/ALT ≤ 5x the upper limit of normal for age
- Serum creatinine < 1.0 mg/dL or 2x the upper limit of normal for age (whichever is
higher)
- Pulse oximetry of > 90% on room air
Recipient Exclusion to administer cells:
- Patients with uncontrolled infections
- Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal
antibodies within 28 days prior to TAA CTL infusion
- GVHD > grade 2 or chronic GVHD manifestations: bronchiolitis obliterans syndrome,
sclerotic GVHD, or serositis
- Pregnant or lactating females
We found this trial at
1
site
111 Michigan Ave NW
Washington, District of Columbia
Washington, District of Columbia
(202) 476-5000
Phone: 202-476-2800
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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