Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 7 for:    26027431 [PUBMED-IDS]

Check Point Inhibition After Autologous Stem Cell Transplantation in Patients at High Risk of Post Transplant Recurrence (CPIT001)

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: NCT02681302
Recruitment Status : Recruiting
First Posted : February 12, 2016
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
Hackensack Meridian Health

Brief Summary:
The goal of this study is to determine the safety and clinical effect of combined checkpoint inhibition administered after autologous hematopoietic stem cell transplantation in each of six clinical cohorts of high risk and recurrent disease. In addition to assessing the incidence and severity of adverse events and rates of complete response and progression free survival, investigators intend to monitor immune reconstitution, phenotype and TCR repertoire throughout treatment and at the time of disease progression. Investigators will also analyze the gut microbiome prior to conditioning, throughout treatment, post-transplant and at time of relapse.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Lymphoma Drug: Ipilimumab Drug: Nivolumab Phase 1 Phase 2

Detailed Description:

This is a phase Ib-IIA study of post-transplant combined check point inhibitors for patients with a high risk of relapse (>50%) after an autologous hematopoietic stem cell transplant.

Patients will accrue to study by disease groups and followed separately by group for incidence and severity of toxicity, ability to receive intended schedule of combined check point inhibitors and for complete response and progression free survival (PFS) rates. Complete response and progression free survival rates will be compared to published standards for each disease group. Expected PFS at 18 months for all post-transplant groups without check point inhibitors is less than 50%. Each group with PFS at 18 months in 4 or more patients (57%) will be considered for eligibility in a successor phase IIB expansion trial.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib-IIA Study of Combined Check Point Inhibition After Autologous Hematopoietic Stem Cell Transplantation in Patients at High Risk for Post-transplant Recurrence
Actual Study Start Date : June 7, 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : March 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: All Participants
  • Ipilimumab 1 mg/kg; 6 doses Weeks 1, 4, 7, 10, 16, 22
  • Nivolumab 3 mg/kg; 12 doses Weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26
Drug: Ipilimumab
1 mg/kg; 6 doses Weeks 1, 4, 7, 10, 16, 22
Other Name: Yervoy

Drug: Nivolumab
3 mg/kg; 12 doses Weeks 1, 4, 7, 10, 12, 14, 16, 18, 20, 22, 24, 26
Other Name: Opdivo




Primary Outcome Measures :
  1. Safety of combined check point inhibition therapy via assessment of adverse events and lab findings [ Time Frame: 26 weeks ]
    To assess the safety of combined check point inhibition with nivolumab and ipilimumab after autologous hematopoietic stem cell transplantation in patients at high risk for post-transplant recurrence including patients with persistent and recurrent high risk diffuse large B cell lymphoma, high risk and recurrent T cell lymphoma and high risk and recurrent multiple myeloma



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 to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and local guidelines.
  2. Be 18 years or older and 80 years or younger on the day of signing consent
  3. Have a confirmed diagnosis of:

    • (GROUP A) De novo diffuse large B cell lymphoma that fails to achieve a PET negative complete response to primary rituximab and anthracycline based multi-agent chemotherapy and at least maintains stable disease after salvage chemotherapy or present double/triple hit features defined by overexpression by standard immunohistochemistry of c-MYC plus BCL2 and/or BCL6 or presence of chromosomal translocations as detected by break-apart FISH involving IGH/MYC plus IGH/BCL2 and/or IGH/BCL6 and who only received standard chemoimmunotherapy with rituximab, cyclophosphamide, vincristine and prednisone (R-CHOP) for induction and present at least stable disease after consolidation or salvage chemotherapy. Stable disease (SD) for lymphoma is defined in Appendix B: Lugano Classification for Response Assessment of Non-Hodgkin Lymphoma.
    • (GROUP B) Recurrent high-risk diffuse large B cell lymphoma defined as relapsing within one year of completion of rituximab and anthracycline based multi-agent chemotherapy or a sAAIPI (second-line age-adjusted International Prognostic Index) intermediate or high at relapse or acquisition of double/triple hit features upon relapse (as defined in group A) and at least stable disease after salvage chemotherapy. Patients with an initial diagnosis of low-grade/indolent non-Hodgkin lymphoma (i.e. follicular, marginal zone) who present relapse with histologic transformation to diffuse large B cell lymphoma (confirmed by biopsy) and meet the definition for high-risk as presented above, are also eligible.
    • (GROUP C) De novo high-risk T cell lymphoma with at least stable disease after primary therapy. High risk T cell lymphoma is defined as Stage III or IV disease at presentation and/or failure to achieve CR after frontline chemotherapy. Patients with ALK-positive ALCL will be excluded from the trial. Patients with ALK-negative ALCL in complete response will be excluded from the trial.
    • (GROUP D) Recurrent T cell lymphoma with at least stable disease after salvage therapy. Patients with ALK-positive ALCL will be excluded from the trial.
  4. Be deemed eligible for an autologous stem cell transplantation according to the institutional guidelines of the Blood and Marrow Transplantation Program at John Theurer Cancer Center at Hackensack University Medical Center
  5. Have an ECOG performance status of 2 or lower
  6. Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
  7. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should agree to ongoing pregnancy testing, to be performed prior to each dosing of ipilimumab and nivolumab. See Note below for definition of WOCBP.
  8. Women must not be breastfeeding.
  9. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab, and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product, even if they have had a vasectomy. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception). See Note below for definition of WOCBP.
  10. Females of childbearing potential must be willing to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 2 years. See Note below for definition of WOCBP.
  11. Allowable transplant preparative regimens are the following:

    • For non-Hodgkin lymphoma groups (A, B,C,D) BEAM: carmustine 300 mg/m2 day -6, etoposide 200 mg/m2 and cytarabine 200 mg/m2 days -5 to -2, melphalan 140 mg/m2 day -1
    • For Myeloma groups (E and F) Melphalan 200 mg/m2 day -1

Exclusion Criteria:

  1. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks 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. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
  2. Is unable or unwilling to sign informed consent.
  3. Has an active, known, or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  4. Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
  5. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
  6. Has received an allogeneic stem cell transplant.
  7. Has a history of hypersensitivity to nivolumab, ipilimumab, or any of its excipients, or severe hypersensitivity reaction to any previous monoclonal antibody.
  8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Day 1 of checkpoint inhibitor treatment administration or who has not recovered (i.e., t administration mAb) within 4 weeks prior to dose of trial treatment. Rituximab within that period is allowed.
  9. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Note: Subjects are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment of non-autoimmune conditions (eg, delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
  10. Has known history of, or any evidence of active, non-infectious pneumonitis.
  11. Has an active infection requiring intravenous 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 23 weeks for females and 31 weeks for males after the last dose of trial treatment.
  15. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known acquired immunodeficiency syndrome (AIDS).
  17. Has positive test for Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) indicating acute or chronic infection, as tested for transplant.
  18. Has received a live vaccine within 30 days of planned start of study therapy.

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): NCT02681302


Contacts
Layout table for location contacts
Contact: Mariefel Vendivil 551-996-5828 Marifiel.Vendivil@HackensackMeridian.org
Contact: Andrea Ortega 551-996-3923 Andrea.Ortega@HackensackMeridian.org

Locations
Layout table for location information
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Kristen Gunn, RN, BSN    202-687-4773    keg91@georgetown.edu   
Contact: Julia Varga, RN, MSN    202-687-7354    jmv78@georgetown.edu   
Principal Investigator: Pashna Munshi, MD         
United States, New Jersey
Hackensack University medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Marifiel Vendivil    551-996-5828    Mariefel.Vendivil@HackensackMeridian.org   
Contact: Andrea Ortega    551-996-3923    Andrea.Ortega@HackensackMeridian.org   
Principal Investigator: Alan Skarbnik, MD         
Principal Investigator: Andrew Pecora, MD         
Sub-Investigator: Michele Donato, MD         
Sub-Investigator: Scott Rowley, MD         
Sub-Investigator: Andre Goy, MD         
Sub-Investigator: Rena Feinman, PhD         
Sub-Investigator: David Vesole, MD, PhD         
Sub-Investigator: David Siegel, MD, PhD         
Sub-Investigator: Tatyana Feldman, MD         
Sub-Investigator: Lori Leslie, MD         
Sub-Investigator: Noa Biran, MD         
Sub-Investigator: Melissa Baker, APN         
Sub-Investigator: Phyllis McKiernan, APN         
Sub-Investigator: Mary DiLorenzo, APN         
Sub-Investigator: Amy Pierre, APN         
Sub-Investigator: Susan Kumka, APN         
Sponsors and Collaborators
Hackensack Meridian Health
Investigators
Layout table for investigator information
Principal Investigator: Alan Skarbnik, MD Hackensack Meridian Health

Publications:
Antonia SJ, Bendell JC, Taylor MH. Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. ASCO Annual Meeting. 2015.
Hodi FS, Sznol M, Kluger HM, McDermott DF, Carvajal RD, Lawrence DP. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;32(Supplement):9002.

Layout table for additonal information
Responsible Party: Hackensack Meridian Health
ClinicalTrials.gov Identifier: NCT02681302     History of Changes
Other Study ID Numbers: 2016-0048
First Posted: February 12, 2016    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: October 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Recurrence
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents