Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Nivolumab and Tocilizumab for Relapsed Hematological Malignancy Post-allogeneic Transplant

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: NCT03588936
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : August 26, 2019
Sponsor:
Information provided by (Responsible Party):
Nirav Shah, Medical College of Wisconsin

Tracking Information
First Submitted Date  ICMJE July 4, 2018
First Posted Date  ICMJE July 17, 2018
Last Update Posted Date August 26, 2019
Actual Study Start Date  ICMJE September 14, 2018
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
Maximum Tolerated Dose among Two Candidate Doses of Nivolumab in Combination with Tocilizumab [ Time Frame: Up to 4 weeks after last dose of study treatment (approximately 3 months) ]
Determine the safety and the maximum tolerated dose among two candidate doses of nivolumab in combination with tocilizumab for treatment of relapsed hematological malignancy post-allogeneic transplant. This will be measured by the number of adverse events as defined by the NCI CTCAE version 4.03 non-hematologic ≥ grade 3-5 signs/symptoms or by the development of steroid refractory grade 2-4 graft-versus-host disease or severe chronic graft-versus-host disease
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03588936 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 21, 2019)
  • Response Rates [ Time Frame: Evaluate at the end of study treatment (approximately 2 months) ]
    Since patients with a variety of histologies will be treated - response will be assessed using disease appropriate imaging/marrow and international consensus criteria most applicable to the disease.
  • Overall Survival [ Time Frame: Up to 1 year from beginning of treatment ]
    Will measure survival of patients after treatment
  • Progression Free Survival [ Time Frame: Up to 1 year from beginning of treatment ]
    Determine the number of patients alive and in remission after treatment
  • Duration of response in responding patients [ Time Frame: Up to 1 year from the beginning of treatment ]
    Time that a patient's disease remains stable
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2018)
  • Response Rates [ Time Frame: Evaluate at the end of study treatment (approximately 2 months) ]
    Since patients with a variety of histologies will be treated - response will be assessed using disease appropriate imaging/marrow and international consensus criteria most applicable to the disease.
  • Overall Survival [ Time Frame: Up to 1 year from beginning of treatment ]
    Will measure survival of patients after treatment
  • Progression Free Survival [ Time Frame: Up to 1 year from beginning of treatment ]
    Determine the number of patients alive and in remission after treatment
  • Duration of response in responding patients [ Time Frame: Up to 1 year from the beginning of treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nivolumab and Tocilizumab for Relapsed Hematological Malignancy Post-allogeneic Transplant
Official Title  ICMJE Phase 1 Study of Nivolumab in Combination With Tocilizumab for Treatment of Patients With Relapsed Hematological Malignancies Post-allogeneic Transplant
Brief Summary This is a phase 1, interventional single arm, open label, treatment study designed to evaluate the safety combination PD-1 and IL-6 inhibition in patients with relapsed disease post-allogeneic transplant.
Detailed Description

Study disease: Hematologic malignancies including, but not exclusive to,acute/chronic leukemia, lymphoma, and myelodysplastic syndrome that has relapsed after allogeneic transplant.

Study Rationale: Phase 1 Safety/Dose Finding Study: To determine the safety and maximum tolerated dose of Nivolumab in combination with Tocilizumab.

Study Agent Description:

Tocilizumab is a monoclonal antibody and immunosuppressant; specifically, tocilizumab is an interleukin-6 (IL-6) receptor antagonist.

Nivolumab is a human immunoglobulin IgG4 monoclonal antibody that binds to the PD-1 receptor of T cells blocking its interaction with PD-L1 and PD-L2, thereby enhancing T-cell proliferation and allowing the immune system to attack the tumor.

Number of Subjects: A maximum of 12 patients will be enrolled on this Phase 1 study.

Duration of Follow-up: Patients will be followed for up to one year post-treatment for survival and response.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Leukemia
  • Chronic Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
Intervention  ICMJE
  • Drug: Nivolumab
    Patients will receive Nivolumab at one of two dose levels every 2 weeks for 4 treatments.
    Other Name: OPDIVO
  • Drug: Tocilizumab
    Patients will receive 2 doses of tocilizumab
    Other Name: ACTEMRA
Study Arms  ICMJE Experimental: Nivolumab and Tocilizumab

Patient will receive tocilizumab 8 mg/kg IV (max dose 800 mg) on Day 0. On Day 1 patients will receive nivolumab IV (0.25 mg/kg or 0.5 mg/kg based on dose escalation design).

Nivolumab will be given every ~2 weeks for up to 4 doses and a second dose of Tocilizumab will be given on ~Day 29 on the same day as Dose # 3 of Nivolumab.

Interventions:
  • Drug: Nivolumab
  • Drug: Tocilizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 1, 2022
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  1. Age≥18 years with hematological malignancies who have undergone allogeneic transplant for hematological malignancy and are ≥180 days post-transplant.
  2. Relapsed disease post-allogeneic transplant defined as follows i. Acute or Chronic Leukemia or myelodysplastic or myeloproliferative disorders or NK cell neoplasms: Bone marrow (BM) with ≥5% disease involvement or peripheral blood evidence of overt relapse ii. Lymphoma: BM evidence of relapsed/persistent disease or PET/CT or CT evidence of persistent/progressive lymphadenopathy consistent with active lymphoma. Active disease defined as nodal lesions ≥ 20 mm in the long axis or extranodal lesions≥10 mm in long and short axis or bone marrow involvement that is biopsy proven
  3. Karnofsky performance status ≥70 (See Appendix A for details)
  4. Creatinine Clearance≥60 ml/min
  5. Adequate hepatic function, defined as AST and ALT ≤3 x ULN. Serum bilirubin and alkaline phosphatase ≤3x x ULN, or considered not clinically significant (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
  6. Without evidence of active acute or chronic GVHD
  7. Off all immunosuppression and corticosteroids (other than replacement dose steroids defined as equivalent to a maximum of 10 mg Prednisone daily) for ≥28 days from first treatment.
  8. Off all disease targeted treatments for ≥10 days to first treatment day
  9. Able to provide written informed consent
  10. Women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and for 120 days after the last treatment with nivolumab.
  11. No FDA approved, more appropriate therapies available for disease control as determined by the treating physician

Exclusion Criteria

  1. Positive beta-HCG in female of child-bearing potential
  2. CD3 donor chimerism <5% within 4 weeks of starting study treatment
  3. Prior administration of donor lymphocyte infusion post-allogeneic transplant within the last 6 months of study treatment
  4. History of or active autoimmune disease, or other syndrome that requires systemic steroids.
  5. History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab.
  6. Uncontrolled or active infections on treatment
  7. Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
  8. Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5 from any previous treatment unless it is felt to be due to underlying disease.
  9. Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution.

    a. Minimum of 4 weeks from last dose of investigational agent

  10. Prior exposure to PD-1 or CTLA4 antibodies in the post-allogeneic transplant setting. Patients who received such agents pre-allogeneic transplant will NOT be excluded.
  11. Prior exposure to daratumumab in the post-allogeneic transplant setting within 2 months of start date of treatment with this investigational protocol. Patients who received this agent pre-allogeneic transplant will NOT be excluded
  12. Concurrent therapies targeted at disease relapse. However, previous treatments for relapsed disease are allowed.
  13. Concurrent active malignancy (exceptions: treated solid malignancy in >2 years' remission, treated basal or squamous cell carcinomas of the skin)
  14. History of Crohn's disease or ulcerative colitis
  15. History of demyelinating disorder
  16. Prior intolerance or allergy to Tocilizumab
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical College of Wisconsin Cancer Center Clinical Trials Office 414-805-8900 cccto@mcw.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03588936
Other Study ID Numbers  ICMJE PRO32525
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Nirav Shah, Medical College of Wisconsin
Study Sponsor  ICMJE Medical College of Wisconsin
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Nirav Shah, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP