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CMP-001 for Relapsed and Refractory Lymphoma

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ClinicalTrials.gov Identifier: NCT03983668
Recruitment Status : Not yet recruiting
First Posted : June 12, 2019
Last Update Posted : June 12, 2019
Sponsor:
Collaborators:
Checkmate Pharmaceuticals
Merck Sharp & Dohme Corp.
University of Iowa
Information provided by (Responsible Party):
Umar Farooq, University of Iowa

Tracking Information
First Submitted Date  ICMJE June 10, 2019
First Posted Date  ICMJE June 12, 2019
Last Update Posted Date June 12, 2019
Estimated Study Start Date  ICMJE July 31, 2019
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2019)
  • Dose limiting toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: From the start of treatment up to two years ]
    To examine the toxicity related to the therapy by measuring the number of treatment related adverse events in patients
  • Objective response rate with statistical analysis based on the EffTox method [ Time Frame: From the start of treatment up to two years ]
    The primary statistical analysis is based on the EffTox method of Thall and Cook (Thall and Cook 2004 [1], Thall, et al 2014 [2]). An adaptive escalation schema is used to find a dose with optimal clinical efficacy and acceptable toxicity. The design has a minimum sample size of 3 patients and a maximum of 39.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CMP-001 for Relapsed and Refractory Lymphoma
Official Title  ICMJE Phase I/II Study of Pembrolizumab and In-situ Injection of CMP-001 in Patients With Relapsed and Refractory Lymphomas
Brief Summary This study is a single-arm, open-label, phase I/II trial designed to find a CMP-001 dose that, in combination with pembrolizumab, has optimal clinical efficacy and acceptable toxicity for patients with relapsed and refractory lymphomas.
Detailed Description This is a single center, open-label, combined Phase I/II clinical study of intratumoral administration of CMP-001 and intravenous administration of pembrolizumab in selected participants with lymphoma. The key study objective is to find a CMP-001 dose that in combination with pembrolizumab has optimal clinical efficacy and acceptable toxicity. Dose-finding will be performed with an adaptive clinical trial design. Secondary study objectives include characterization of safety, pharmacodynamics, and assessment of anti-lymphoma activity.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Drug: CMP-001
    Immunostimulatory therapeutic agent
    Other Name: CYT003; QbG10; IND # 18627
  • Drug: Pembrolizumab
    Humanized antibody used in cancer immunotherapy
    Other Name: Keytruda
Study Arms  ICMJE Experimental: CMP-001 plus pembrolizumab
Intratumoral administration of CMP-001 and intravenous administration of pembrolizumab
Interventions:
  • Drug: CMP-001
  • Drug: Pembrolizumab
Publications *

*   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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 10, 2019)
39
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 1, 2022
Estimated Primary Completion Date April 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

  • Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of relapsed or refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma (B and T cells).
  • Male participants: A male participant must agree to use a contraception as detailed in Appendix C of this protocol during the treatment period and for at least five months after the final CMP-001 and pembrolizumab dose and refrain from donating sperm during this period.
  • Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix C), not breastfeeding, and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix C OR
    2. A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the treatment period and for at least 5 months after the last dose of study treatment.
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial prior to the initiation of any study procedures. The participant must be capable of understanding and complying with protocol requirements.
  • Have measurable disease based on Cheson 2007 (Cheson, et al 2007). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Subjects must have at least one tumor lesion with a longest diameter of ≥ 1 cm that can be easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 (eg, tumor in skin, muscle, subcutaneous tissue or accessible lymph node).
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation/randomization.

Exclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of study drug. (see Appendix C). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) within 4 weeks of enrollment into this trial.
  • Has received prior systemic anti-cancer therapy including investigational agents within 2 weeks or 5 half-lives whichever is shorter, prior to first dose of study drug.

Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.

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

  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 2 weeks or within 5 half-lives whichever is shorter, prior to the first dose of study treatment.

Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 2 weeks or within 5 half-lives whichever is shorter, after the last dose of the previous investigational agent.

  • Has a diagnosis of primary immunodeficiency disorder or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  • 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.
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Patients with allotransplant in past 5 years or those with evidence of graft vs. host disease (GVHD) will be excluded.
  • Have inadequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days prior to the start of study treatment.

    1. Hematological: Absolute neutrophil count (ANC) ≥1000/µL;Platelets ≥75 000/µL; Hemoglobin ≥8.0 g/dLa;
    2. Renal: Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN;
    3. Hepatic: Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases);
    4. Coagulation: International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants;

ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.

a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.

b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

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: Umar Farooq, MD 319-384-8044 umar-farooq@uiowa.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03983668
Other Study ID Numbers  ICMJE 201902747
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Umar Farooq, University of Iowa
Study Sponsor  ICMJE Umar Farooq
Collaborators  ICMJE
  • Checkmate Pharmaceuticals
  • Merck Sharp & Dohme Corp.
  • University of Iowa
Investigators  ICMJE
Principal Investigator: Umar Farooq, MD University of Iowa
PRS Account University of Iowa
Verification Date June 2019

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