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Trial record 1 of 1 for:    NCT04094961
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Ixazomib + Pomalidomide + Dexamethasone In MM

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ClinicalTrials.gov Identifier: NCT04094961
Recruitment Status : Recruiting
First Posted : September 19, 2019
Last Update Posted : April 15, 2022
Information provided by (Responsible Party):
Paul G. Richardson, MD, Dana-Farber Cancer Institute

Brief Summary:
This is a Phase I/II study using the combination of twice weekly ixazomib plus pomalidomide and dexamethasone in relapsed and or refractory multiple myeloma (RRMM) patients.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Multiple Myeloma in Relapse Drug: Ixazomib Drug: Pomalidomide Drug: Dexamethasone Phase 1 Phase 2

Detailed Description:

This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational drug and tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.

The FDA has approved both pomalidomide and ixazomib individually for the treatment of multiple myeloma. Dexamethasone, also FDA approved, is a type of steroid and is usually combined with other chemotherapy for the treatment of blood cancers, such as myeloma and leukemias.

  • Ixazomib targets a part of cells called proteasomes. It works by slowing down or blocking proteasomes from doing their job of digesting proteins. In myeloma cells, there is a greater need for proteasomes to digest proteins; the buildup of excess proteins causes cell death.
  • Pomalidomide has also been shown to cause tumor cell deaths. Dexamethasone can stop white blood cells from traveling to areas myeloma cells are causing damage. When combined with myeloma drugs, it sometimes makes those drugs work better.

In this research study, the investigators are:

  • Testing the safety of ixazomib when given with pomalidomide and dexamethasone
  • Pomalidomide and ixazomib are given individually for the treatment of multiple myeloma. Dexamethasone is also given for multiple myeloma
  • Ixazomib when combined with pomalidomide and dexamethasone may help control the disease
  • Ixazomib is FDA approved to treat multiple myeloma
  • The investigators are looking for the highest dose of ixazomib that can be given safely in combination with pomalidomide and dexamethasone

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Twice Weekly Ixazomib Plus Pomalidomide and Dexamethasone in Relapsed/or Refractory Multiple Myeloma
Actual Study Start Date : September 18, 2019
Estimated Primary Completion Date : March 20, 2024
Estimated Study Completion Date : March 20, 2024

Arm Intervention/treatment
Experimental: ixazomib plus pomalidomide and dexamethasone

The study drugs will be administered within a 21-day cycle

  • Phase I will follow a standard "3 +3" dose escalation design: Starting with the first cohort, 3 to 6 patients will be treated at this and each subsequent dose level.
  • The Phase II portion of the study will be a single-arm open-label enrollment with dosing based on the MTD determination in the Phase I portion of the study
Drug: Ixazomib
Oral, administered four times per cycle
Other Name: Ninlaro®

Drug: Pomalidomide
Oral, administered 14 times per cycle
Other Name: Pomalyst®

Drug: Dexamethasone
Oral, fixed dose administered 8 times per cycle
Other Names:
  • Baycadron
  • Decadron
  • Dexamethasone Intensol
  • DexPak
  • TaperDex
  • Zema-Pak
  • ZoDex
  • Zonacort

Primary Outcome Measures :
  1. Number of participants with dose limiting toxicity [ Time Frame: 21 Days ]
    3 - 24 safety evaluable patients will be enrolled in up to 4 dose levels of ixazomib, pomalidomide and dexamethasone.

  2. Overall Response Rate [ Time Frame: 28 days ]
    Response will be evaluated using a Simon optimal two-stage design

Secondary Outcome Measures :
  1. Time to Progression [ Time Frame: time from first dose of study drug to progression, censored at date last known progression-free for those who have not progressed, whichever came first, assessed up to 60 months ]
    Estimated using the method of Kaplan-Meier.

  2. Progression Free Survival [ Time Frame: time from first dose of study drug to the disease progression or death from any cause, censored at date last known progression-free for those who have not progressed or died, whichever came first, assessed up to 60 months ]
    Estimated using the method of Kaplan-Meier.

  3. Duration of Response [ Time Frame: time from response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died, whichever came first, assessed up to 60 months ]
    Estimated using the method of Kaplan-Meier.

  4. Overall Survival [ Time Frame: time from first dose of study drug to death or date last known alive, whichever came first, assessed up to 60 months ]
    Estimated using the method of Kaplan-Meier.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • Patients with relapsed and relapsed refractory myeloma may be eligible for this trial of they meet all the following entry criteria.
  • Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.
  • Patient has given voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
  • Patient had received at least two previous therapies OR received 1 prior line of therapy if previously treated with an IMiD plus a proteasome inhibitor and has demonstrated disease progression on or within 60 days of completion of the last therapy
  • Patient has measurable disease defined as at least one of the following according to Standard Diagnostic Criteria (Rajkumar 2014):

    • Serum IgG, IgA, or IgM M-protein ≥ 0.5 g/dL, or
    • Serum IgD M-protein ≥ 0.05 g/dL, or
    • Urine M protein ≥200 mg/24 hours or
    • Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
    • Screening Laboratory evaluations within the following parameters

      • Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L) (Growth factors cannot be used more recently than 14 days prior to initiation of therapy)
      • Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 14 days prior to initiation of therapy)
      • Hemoglobin ≥ 8.0 g/dl (RBC transfusions are permitted)
      • Total Bilirubin ≤ 1.5 X upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
      • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
      • Calculated creatinine clearance ≥ 45 mL/min
    • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
    • All study participants must be registered into the mandatory POMALYST REMS® program, and be willing and able to comply with the requirements of the POMALYST REMS® program.
    • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program.
    • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Prior exposure to ixazomib OR is refractory to pomalidomide
  • Patients that have previously been treated with ixazomib, or participated in a study with ixazomib,whether treated with the agent or not, are also excluded
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.
  • Diagnosed or treated for another malignancy within 3 years prior to enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low risk prostate cancer after curative therapy.
  • Known GI disease or is in need of, or has had a previous GI procedure that could interfere with the oral absorption or tolerance of ixazomib or pomalidomide including difficulty swallowing.
  • Known central nervous system involvement.
  • Systemic treatment, within 14 days before the first dose of treatment, with strong CYP3A or inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort OR systemic treatment within 14 days of the first dose of treatment with a strong inhibitor of CYP1A2 (ciprofloxacin, fluvoxamine, cimetidine, enoxacin, ethynyl estradiol, mexiletine)
  • Any medical or psychiatric illness/social situation that in the Investigator's opinion, would impose excessive risk to the patient, would adversely affect his/her participating in this study or would limit compliance with study requirements.
  • Any active, or uncontrolled cardiovascular conditions, including but not limited to uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, grade 3 thromboembolic event or myocardial infarction within the past 6 months.
  • The following therapies within the stated time frames prior to initiation of therapy:

    • Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 21 days (42 days for nitrosoureas).
    • The use of live vaccines within 30 days.
    • ImiDs or proteasome inhibitors within 14 days.
    • Other investigational therapies and/or monoclonal antibodies within 4 weeks.
    • Prior peripheral stem cell transplant within 12 weeks.
    • Prior allogeneic stem cell transplantation with active graft-versus-host-disease.
  • Currently active graft versus host disease of any stage or grade after allogeneic stem cell transplantation
  • Prior major surgical procedure or radiation therapy within 14 days of initiation of therapy.

    • Those who require a limited course of radiation for management of bone pain more than 14 days out from initiation of therapy are not excluded
    • If the involved field is small, 7 days will be considered a sufficient interval between radiotherapy and administration of the ixazomib.
  • Daily requirement for corticosteroids (equivalent to > 10 mg/day prednisone, though >10mg/day is acceptable if physiological levels require, so long as the dose is stable for at least 7 days prior to initiation of therapy. Inhalation corticosteroids are exempt from this criterion.

    -- Lower amounts of corticosteroids that are not part of a daily requirement within 14 days prior to initiating therapy

  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.

    -- Those who are on prophylactic antibiotics only, or on antibiotics and have confirmation of resolution of active infection are eligible.

  • Known seropositive for active viral infection with human immunodeficiency virus (HIV) hepatitis B (HBV) or hepatitis C viral (HCV). Those who are seropositive because of hepatitis B vaccine are eligible. Patients who are positive for HBV core antibody or HBV surface antigen must have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are PCR positive will be excluded
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period
  • Participants who are receiving any other investigational agents for any indication
  • History of erythema multiforme or severe hypersensitivity to prior IMiD's® or those who have a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Inability to tolerate thromboprophylaxis
  • Failure to have fully recovered (≤ Grade 1 according to CTCAE v 5) from the reversible effects of prior chemotherapy
  • Peripheral neuropathy must have resolved to Grade 1 toxicity or peripheral neuropathy grade 2 with no pain to be eligible
  • Alopecia of any grade is eligible

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): NCT04094961

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Contact: Alexandra Savell 617-632-3539 asavell@partners.org

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United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Paul G Richardson, MD    617-632-2104    Paul_Richardson@dfci.harvard.edu   
Principal Investigator: Paul G Richardson, MD         
Sponsors and Collaborators
Paul G. Richardson, MD
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Principal Investigator: Paul Richardson, MD Dana-Farber Cancer Institute
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Responsible Party: Paul G. Richardson, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT04094961    
Other Study ID Numbers: 19-291
First Posted: September 19, 2019    Key Record Dates
Last Update Posted: April 15, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Data can be shared no earlier than 1 year following the date of publication
Access Criteria: DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
URL: http://innovation@dfci.harvard.edu

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Paul G. Richardson, MD, Dana-Farber Cancer Institute:
Multiple Myeloma
Multiple Myeloma in Relapse
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents