A Study to Evaluate Myeloma-Developing Regimens Using Genomics (MyDRUG)

Overview

About this study

The purpose of this study is to treat patients with drugs targeted to affect specific genes that are mutated as part of the disease. Mutations in genes can lead to uncontrolled cell growth and cancer. Patients with a greater than 30% mutation to any of the following genes; CDKN2C, FGFR3, KRAS, NRAS, BRAF V600E, IDH2 or T(11;14) can be enrolled to one of the treatment arms. These arms have treatments specifically directed to the mutated genes. Patients that do not have a greater than 30% mutation to the genes listed can be enrolled to a non-actionable treatment arm. The genetic sequencing of the patient's tumor is required via enrollment to the MMRF002 study: Clinical-grade Molecular Profiling of Patients with Multiple Myeloma and Related Plasma Cell Malignancies. (NCT02884102).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria: 

  • Have enrolled in the MMRF002 Molecular Profiling Protocol (NCT02884102) “companion’ protocol and have a report that is less than 120 days.
  • ≥ 18 years of age.
  • Willing to consent to the assigned Sub-Protocol.
  • Patient meets all entry criteria for the assigned Sub-Protocol.
  • High risk patients with RRMM who have:
    • received at least one prior but no more than 3 prior therapies;
    • exposed to both a PI and an IMiD;
    • had early relapse after initial treatment. Relapse is defined as the IMWG uniform response criteria (Kumar et al, 2016). Early relapse as defined by at least one of the following:
      •  Relapse within 3 years post autologous stem cell transplantation (ASCT) on maintenance, or 18 months if unmaintained;
      • Relapse within 18 months of initial non-ASCT based therapy.
  • Patients must have progressed after their most recent treatment and require therapy for myeloma.
  • The following laboratory values obtained ≤ 14 days prior to registration:
    • ANC ≥ 1000/ul;
    • Hgb ≥ 8 g/dl;
    • PLT ≥ 75,000/ul (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to study drug dosing for any dosing day);
    • Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is >1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL;
    • AST <3 x ULN;
    • Creatinine Clearance ≥ 30 mL/min by Cockroft Gault Equation.
  • Measurable disease of MM as defined by at least ONE of the following:
    • Serum monoclonal protein ≥1.0 g by protein electrophoresis;
    • ≥ 200 mg of monoclonal protein in the urine on 24-hour electrophoresis;
    • Serum immunoglobulin FLC ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio;
    • Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2.
  • Willingness to return to enrolling institution for follow-up.
  • Disease free of prior malignancies for ≥ 3 year with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma “insitu” of the cervix or breast, or prostate cancer not requiring therapy.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
  • Female subjects of childbearing potential must have negative results for pregnancy test.
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following:
  • All study participants must be willing to be registered into the mandatory pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program and be willing and able to comply with the requirements of the POMALYST REMS® program.
    • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug; or 
    • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception);
    • Females of reproductive potential* must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS® program.
  • Ability to understand the purpose and risks of the study and provide signed and dated ICF and authorization to use protected health information.
  • *Female of reproductive potential is any sexually mature female who:
    • has not undergone a hysterectomy or bilateral oophorectomy; or
    • has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Sub-Protocol Inclusion Criteria

  • Refer to each respective Sub Protocol attached to this document for additional inclusion criteria.

EXCLUSION CRITERIA:

Patients will be ineligible for this study if they meet any one of the following criteria:

  • Aggressive multiple myeloma requiring immediate treatment as defined by:
    • LDH > 2 times ULN;
    • Presence of symptomatic extramedullary disease or central nervous system involvement;
    • Hypercalcemia >11.5 mg/dl;
    • Acute worsening of renal function (CrCl < 30 ml/min) directly related to myeloma relapse;
    • Any neurological emergency related to myeloma;
    • Clinical symptoms of hyperviscosity related to monoclonal protein;
    • Involved serum free light chain > 100 mg/dL (1000 mg/L) in the setting of prior diagnosis of cast nephropathy;
    • Primary Refractory Disease (See Appendix E for a definition of Primary Refractory Disease).
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days of enrolment (fist treatment).
  • Known hypersensitivity or development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide, pomalidomide or similar drug. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of the agents.
  • Other co-morbidity, which would interfere with patient's ability to participate in trial or that confounds the ability to interpret data from the study.
  • Prior Ixazomib/Pomalidomide/Dexamethasone combination therapy.
  • Pregnant or breast-feeding females.
  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation.
  • Active hepatitis A, B or C viral infection or known HIV infection.
  • Concurrent symptomatic amyloidosis or plasma cell leukemia.
  • POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes].
  • Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 2 without pain are permitted).
  • Prior allogeneic or ASCT within 12 weeks of initiation of therapy. Prior allogeneic stem cell transplant with active graft-versus-host disease (GVHD).
  • Prior experimental therapy within 14 days of protocol treatment or 5 half-lives of the investigational drug, whichever is longer.
  • Prior anticancer therapy within 14 days of initiation of protocol therapy.Dexamethasone (40mg/day) for a maximum of 4 days before screening is allowed.
  • Prior major surgical procedure or radiation therapy within 4 weeks of the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy).
  • Known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or GI absorption of drugs administered orally.
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers; e.g.:
    • Strong CYP3A inducers - avasimibe,carbamazepine, enzalutamine, mitotane, phenytoin, rifampin, St. John's wort;
    • Moderate CYP3A inducers - bosentan, efavirenz, etravirine, modafinil, nafcillin;
    • Strong CYP3A inhibitors - boceprevir, clarithromycin, cobicistat, conivaptan, danoprevir/ritonavir, elvitegravir/ritonavir, idelalisib, indinavir, itraconazole, ketoconazole, mibefradil, lopinavir/ritonavir, nefazodone, nelfinavir, ritonavir, paritaprevir/ritonavir combinations, posaconazole, saquinavir, telaprevir, telithromycin, tipranavir/ritonavir, voriconazole.
  • Systemic treatment, within 14 days before the first dose of pomalidomide, strong inhibitors of CYP1A2, or use of St. John’s wort.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Patient met one or more exclusion criteria for participation in the Sub-Protocol.

Sub-Protocol Exclusion Criteria

  • Refer to each respective Sub Protocol attached to this document for additional exclusion criteria.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Jeremy Larsen, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Shaji Kumar, M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

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