Tumor Associated Antigen Specific T Cells (TAA-T) With PD1 Inhibitor for Lymphoma

  • STATUS
    Recruiting
  • End date
    Nov 19, 2023
  • participants needed
    18
  • sponsor
    Catherine Bollard
Updated on 19 August 2020
Investigator
Hema Dave, MD
Primary Contact
Children's National Medical Center (5.4 mi away) Contact
+1 other location
lymphoma
hodgkin's disease
granulocyte colony stimulating factor
measurable disease
colony stimulating factor
nivolumab
diffuse large b-cell lymphoma
b-cell lymphoma
pet/ct scan
salvage therapy
brentuximab
pd-1 inhibitor
refractory hodgkin lymphoma

Summary

This is a Phase I, open-label multi-site trial designed to evaluate the safety of administering rapidly-generated Tumor associated antigen specific T cells (TAA-T) with the Programmed Death1 (PD-1) inhibitor Nivolumab, in relapsed/refractory lymphoma (rel/ref) patients with measurable disease (group A) or as adjunctive therapy following autologous hematopoeitic stem cell transplant(HSCT) for patients at high risk of relapse (group B).

The purpose of this study is to find out if the tumor specific T cells given with Nivolumab are safe and to learn what the side effects are and if the combination can help patients with relapsed lymphomas.

Description

This Phase I, open-label multi-site trial is designed to evaluate the safety of administering rapidly-generated multi-antigen-specific T lymphocytes with the PD1 inhibitor Nivolumab, to relapsed/refractory (rel/ref) lymphoma patients with measurable disease (group A) or as adjunctive therapy following autologous HSCT (group B).

This study will first enroll 6 patients total (in Groups A and B) in the initial safety monitoring or DLT group prior to the expansion phase where additional 12 patients (6 in Group A and 6 in Group B) will be enrolled. TAA-T cells will be generated from patient's lymphocytes obtained from patient's PBMC.

If patient meets eligibility criteria for TAA-T cell infusion, the patient (Group A or Group B) will receive two TAA-T cell infusions given 2 weeks apart, where the expected volume of infusion is 1 to 10 cc.

Both TAA-T cells and Nivolumab will be given at the doses below with allowed de-escalation of both doses as follows:

  • TAA-T cell dose: 2 x 107 cells/m2 per infusion
  • Nivolumab: For patients <18 years, 3 mg/kg/dose (maximum 240mg/dose) every 2 weeks. For adult patients 18 years, a dose of 240mg every 2 weeks or 480mg every 4 weeks

From the first 2 enrolled patients, if at least one patient meets dose limiting toxicity criteria (as described in section 6.4.1) at the above mentioned combination dose level, then the next 2 patients will receive TAA-T cells at 1 x 107 cells/m2 without a change in Nivolumab dose. If toxicity criteria are met by at least one patient from these 2 patients, then the dose of Nivolumab will be reduced to 1mg/kg/dose for patients <18 years or 100mg if receiving 240mg dosing or 200mg if receiving 480mg dosing for adult patients 18 years for next 2 patients and TAA-T cells will be given at the same de-escalated dose of 1x 107 cells/m2.

In case the patient experiences toxicity from Nivolumab prior to the first TAA-T cell infusion, they can receive the TAA-T cells after resolution of the Nivolumab toxicities and steroid dosing has been reduced less than 0.5mg/kg/day.

After the safety phase is complete, additional 12 patients total will be enrolled on expansion cohort.

Patients will receive doses Nivolumab at a minimum of 8 weeks prior to first TAA-T cell infusion and additional dose(s) of Nivolumab will be given after 4 weeks following second TAA-T cell infusion starting at week 7 from first infusion of TAA-T.. Delays >3 days for the Nivolumab will not be considered protocol violations if discussed with the PI.

If the TAA-T cells are not ready after the initial doses of Nivolumab prior to the first TAA-T infusion, then the patients can continue Nivolumab infusions for an additional 8 weeks at the PI's discretion. If there is insufficient number of TAA-Ts for the two planned infusions, then additional blood may be drawn and patients can continue on Nivolumab unless they rapidly progress with disease requiring urgent therapy. If there is insufficient number of TAA-Ts to meet study dose, a lower dose of TAA-T may be infused at the discretion of the PI.

Only group A patients are eligible for additional doses ( 3 to 8) if they have stable disease or response, do not have grade 3 toxicity attributed to TAA-T cells and do not have clinical evidence of rapidly progressing disease requiring urgent therapy.

For Group B patients, blood for generation for TAA-T cells (non-mobilized) will be collected prior to the stem cell collection or any time after Day 30 post auto-HSCT. Treatment with Nivolumab will begin any time after Day 30 post auto-HSCT. Patients are eligible for Group B if they have no evidence of metabolically active disease by PET/CT (Deauville Score of 3 or less) at time of starting treatment with Nivolumab. Patients eligible for Group B with <CMR)/CR (by PET/CT) prior to auto-HSCT will need to be in CR (Deauville Score of 3 or less) prior to the start of Nivolumab or can be moved to Group A if they have metabolically active disease (Deauville Score of 4 or more) by PET/CT.

Patients should not receive other systemic antineoplastic agents including Nivolumab for at least 6 weeks after the first infusion of TAA-specific T-cells (for purposes of evaluation), although such treatment may be added if deemed critical for patient care by the attending physician.

Patients in Group A will not be able to receive additional doses (3-8) of TAA-T cells until the initial 6 weeks evaluation for toxicity and efficacy following the first TAA-T cell infusion.

Patients (Group A and B) will not receive subsequent doses of Nivolumab until the safety evaluation for TAA-T is over (at least 6 weeks from the first infusion).

Details
Treatment Nivolumab, TAA-T cells
Clinical Study IdentifierNCT03843294
SponsorCatherine Bollard
Last Modified on19 August 2020

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Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 12 yrs and 80 yrs?
Gender: Male or Female
Do you have any of these conditions: Lymphoma or Hodgkin's Disease or Diffuse Large B-Cell Lymphoma?
Group A (patients with measurable disease) Relapsed/Refractory Hodgkin
Lymphoma (HL) and Diffuse Large B cell Lymphoma (DLBCL) DLBCL
Patients with Primary Treatment Failure (PTF) and one or more Ultra-high risk (UHR) features, no prior salvage treatment required. Please refer to Appendix A for definitions of PTF and UHR
Rel/ref DLBCL failing 1st salvage treatment (Progressive disease (PD)/ Stable Disease (SD)/Partial Response (PR))
Rel/ref DLBCL without acceptable treatment options in the opinion of the treating physician HL
Rel/ref HL failing more than or equal to 1 salvage regimens, including prior Brentuximab Vedotin (BV)
Rel/ref after autologous HSCT
Group B (consolidation after auto-HSCT for patients at high risk for relapse)
DLBCL
Patients with < CMR/CR (by PET/CT) with initial treatment regimen
Patients with relapse <12 months from diagnosis or <6 months from completion of initial therapy
Patients with <CMR/CR (by PET/CT) prior to autologous HSCT
Patients requiring >1 salvage regimen prior to autologous HSCT HL
Patients not eligible for post auto-HSCT consolidation with Brentuximab AND
Patients with relapse <12 months from diagnosis or <6 months from completion of initial therapy
Patients with <CMR/CR (by PET/CT) prior to autologous HSCT
Patients requiring >1 salvage regimen prior to autologous HSCT
Recipient Inclusion Criteria for Initial and Subsequent Procurements (TAA-T
Cell Generation)
Age 12 years to 80 years
Karnofsky/Lansky score of more than or equal to 50 (see appendix C)
ALC > 600
Patients receiving Granulocyte colony-stimulating factor (G-CSF) are recommended a washout period of a minimum of two weeks before procurement
Agree to use contraceptive measures during study protocol participation (when age appropriate)
Patient or parent/guardian capable of providing informed consent
Recipient Exclusion Criteria for Initial and Subsequent Procurements (TAA-T
Cell Generation)
Prior allogeneic BMT
Prior solid organ transplant
Patient who has received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days of screening for enrollment
Patient with uncontrolled infections
Patient with active HIV
Pregnancy or lactating
Failure to meet institutional guidelines for treatment with Nivolumab
Recipient Inclusion Criteria for Initial and Subsequent TAA-T Cell Infusions
Age 12 years to 80 years
Patient has received at least 8 weeks of Nivolumab
Patients with Grade 1 toxicities attributed to Nivolumab will be eligible at the discretion of the PI. Toxicities include but not limited to: laboratory abnormalities in thyroid function tests suggestive of hypothyroidism, thyroiditis or thyroid dysfunction adequately managed with thyroid hormone replacement, or abnormalities in amylase, lipase
Steroids less than 0.5 mg/kg/day prednisone or equivalent
Karnofsky/Lansky score of more than or equal to 50
Pulse oximetry of > 90% on room air
Bilirubin less than or equal to 2.5 mg/dL, AST/ALT less than or equal to 5x upper limit of normal, serum creatinine < 1.0 or 2x the upper limit of normal (whichever is higher)
Absolute neutrophil count > 250/L (may be supported with GCSF)
Agree to use contraceptive measures during study protocol participation (when age appropriate)
Patient or parent/guardian capable of providing informed consent

Exclusion Criteria

Investigational therapies within 28 days prior to screening for enrollment
Uncontrolled infections
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