Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nivolumab/Ipilimumab-Primed Immunotransplant for DLBCL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03305445
Recruitment Status : Recruiting
First Posted : October 10, 2017
Last Update Posted : May 10, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Joshua Brody, Icahn School of Medicine at Mount Sinai

Brief Summary:
This multi-center study open-label trial will enroll a single cohort of relapsed/refractory diffuse large B cell lymphoma (DLBCL) patients whom are ineligible for autologous stem cell transplant (ASCT) due to 1) insensitivity to salvage chemotherapy, or 2) inability to tolerate high-dose myeloablative chemotherapy. All patients will receive dual checkpoint blocking antibody (DCBA) therapy with established doses currently being used in phase III trials of ipilimumab (1mg/kg) and nivolumab (3mg/kg) given at three week intervals, two times before, and two times following "immunotransplant" in which T cells (in whole PBMCs) are cryopreserved and re-infused (adoptive T cell transfer or ATCT) following lymphodepleting chemotherapy regimen, currently being employed in adoptive T cell therapies.

Condition or disease Intervention/treatment Phase
Relapsed Diffuse Large B-Cell Lymphoma Refractory Diffuse Large B-Cell Lymphoma Drug: Ipilimumab Drug: Nivolumab Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 13 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This multi-center study open-label trial will enroll a single cohort of relapsed/refractory diffuse large B cell lymphoma (DLBCL) patients whom are ineligible for autologous stem cell transplant (ASCT).
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center Phase Ib/II Trial of Nivolumab/Ipilimumab-Primed Immunotransplant for Relapsed/Refractory Diffuse Large B Cell Lymphoma Patients.
Actual Study Start Date : May 14, 2018
Estimated Primary Completion Date : November 27, 2019
Estimated Study Completion Date : November 27, 2019


Arm Intervention/treatment
Experimental: Pts with Diffuse Large B Cell Lymphoma
Patients with DLBCL not eligible for autologous stem cell transplant. All patients will receive dual checkpoint blocking antibody (DCBA) therapy of ipilimumab and nivolumab given at three week intervals, two times before, and two times following "immunotransplant" in which T cells (in whole PBMCs) are cryopreserved and re-infused (adoptive T cell transfer or ATCT) following lymphodepleting chemotherapy regimen, currently being employed in adoptive T cell therapies.
Drug: Ipilimumab
Ipilimumab (1mg/kg)
Other Name: Yervoy

Drug: Nivolumab
Nivolumab (3mg/kg)
Other Name: Opdivo




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: 3 months ]
    DLTs recorded and graded according to NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. for Phase 1B part of study

  2. Completion Remission (CR) Rate [ Time Frame: 3 months ]
    The proportion of patients who have achieved complete remission as per Lugano criteria which is complete metabolic response even with a persistent mass.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 2 years ]
    PFS will be estimated using the method of Kaplan-Meier where PFS is defined as the time from Adoptive T cell transfer (ATCT) until the first recurrence or progression of disease as per Lugano criteria (3), or date of death if the subject dies from any cause before progression is documented.

  2. Overall Survival (OS) [ Time Frame: 2 years ]
    OS from the time of ATCT (D0) until recorded date of death.

  3. IgVH level [ Time Frame: 2 years ]
    Rate and time to achieving molecular remission as determined by serum analysis for persistent IgVH by PCR

  4. Delayed CR [ Time Frame: 2 years ]
    Delayed CR defined as the proportion of patients who achieved CR reported as a percentage of the total number of subjects enrolled for both FA and PP populations.

  5. Overall Response Rate (ORR) [ Time Frame: 2 years ]
    ORR, defined as CR+PR+SD (complete remission + partial remission + stable disease



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Have pathologically confirmed DLBCL on biopsy.
  2. Be willing and able to provide written informed consent/assent for the trial.
  3. Be ≥18 years of age on day of signing informed consent
  4. Have a performance status of 0, 1, or 2 on the ECOG Performance Scale
  5. Demonstrate adequate organ function at time of screening as defined in Table 2 below, all screening labs should be performed within 14 days of treatment initiation.

    Table 2 Adequate Organ Function Laboratory Values System Laboratory Value Hematologica Absolute neutrophil count (ANC) ≥1,000 /mcL Platelets ≥25,000 / mcL Hemoglobin ≥8 g/dL Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤2.0 X upper limit of normal (ULN) OR

    ≥60 mL/min for subject with creatinine levels > 2.0 X institutional ULN Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR

    ≤ 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)

    Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT is within therapeutic range of intended use of anticoagulants

    ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PTT is within therapeutic range of intended use of anticoagulants a Patients with cytopenias attributable to bone marrow lymphomatous bone marrow involvement per current bone marrow biopsy may be enrolled if other inclusion criteria are met.

    b Creatinine clearance should be calculated per institutional standard.

  6. Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of DCBA. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  7. Female subjects of childbearing potential must be willing to use an adequate method of contraception. Contraception should be used for the course of the study through 120 days after the last dose of study medication.

    Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

  8. Male subjects of childbearing potential must agree to use an adequate method of contraception. Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  9. Patients who did not achieve a PR or CR as per the Lugano criteria following at least 1 cycle of platinum-based salvage chemotherapy, or patients not eligible for platinum-based therapy or BEAM induction therapy due to decreased ejection fraction (<40%).
  10. There is no upper age restriction.
  11. Patients whom have undergone previous autologous stem cell transplant, and have recurrent or residual disease are eligible for this trial.

Exclusion Criteria:

The subject must be excluded from participating in the trial if the subject:

  1. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
  2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  3. Has a known history of active TB (Bacillus Tuberculosis)
  4. Hypersensitivity to ipilimumab or nivolumab or any of their excipients.
  5. Has had a prior anti-cancer monoclonal antibody (mAb) within 28 days prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 28 days earlier.
  6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.

    Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

    Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

  7. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  8. Has known active central nervous system (CNS) metastases and/or lymphomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include lymphomatous meningitis, which is excluded regardless of clinical stability.
  9. Has active autoimmune disease that has required systemic treatment in the past 1 year (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a systemic treatment. Subjects on stable dose of corticosteroids less than or equivalent to 10mg of prednisone daily for more than 3 months may be enrolled, and continue their stable dose through treatment.
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Has an active infection requiring systemic therapy.
  12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment (roughly two and a half years after enrollment).
  15. HIV positive with detectable viral load, or anyone not on stable anti-viral (HAART) regimen.
  16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  17. History of allogeneic stem-cell (or other organ) transplantation.
  18. Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03305445


Contacts
Layout table for location contacts
Contact: Kyutae Kim 212-824-7822 kyutae.kim@mssm.edu
Contact: Johnny Chan 212-824-7861 johnny.chan@mssm.edu

Locations
Layout table for location information
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Kyutae Kim    212-824-7822    kyutae.kim@mssm.edu   
Contact: Johnny Chan    212-824-7861    johnny.chan@mssm.edu   
Principal Investigator: Joshua Brody, MD         
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
Bristol-Myers Squibb
Investigators
Layout table for investigator information
Principal Investigator: Joshua Brody, MD Icahn School of Medicine at Mount Sinai

Layout table for additonal information
Responsible Party: Joshua Brody, Assistant Professor, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT03305445     History of Changes
Other Study ID Numbers: GCO 17-2164
First Posted: October 10, 2017    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joshua Brody, Icahn School of Medicine at Mount Sinai:
Immunotransplant
Relapsed Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Nivolumab
Ipilimumab

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents