Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Daratumumab, Ixazomib, & Dexamethasone or Daratumumab, Bortezomib, & Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma (DeRIVE)

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: NCT03942224
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : December 4, 2019
Sponsor:
Collaborators:
Takeda
Janssen, LP
Information provided by (Responsible Party):
Ajay Nooka, Emory University

Brief Summary:
This phase II trial studies how well daratumumab, ixazomib, and dexamethasone with or without bortezomib work in treating patients with newly diagnosed multiple myeloma. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as ixazomib, dexamethasone, and bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving daratumumab, ixazomib, and dexamethasone with or without bortezomib may work better in treating patients with multiple myeloma.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Drug: Bortezomib Biological: Daratumumab Drug: Dexamethasone Drug: Ixazomib Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 76 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of DaRatumumab, Ixazomib, and Dexamethasone vs Daratumumab, Bortezomib (VElcade) and Dexamethasone Followed by Daratumumab-Ixazomib-Dexamethasone in Newly Diagnosed Multiple Myeloma (DeRIVE Study)
Actual Study Start Date : July 3, 2019
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : July 31, 2024


Arm Intervention/treatment
Experimental: Arm I (DId)

INDUCTION: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2 and on days 1 and 15 of cycles 3-8, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance.

MAINTENANCE: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Biological: Daratumumab
Given IV
Other Names:
  • Anti-cluster of differentiation 38 (CD38) Monoclonal Antibody
  • Darzalex
  • HuMax-CD38

Drug: Dexamethasone
Given IV and PO
Other Names:
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex

Drug: Ixazomib
Given PO
Other Names:
  • Ninlaro
  • MLN2238

Experimental: Arm II (DVd, DId)

INDUCTION CYCLES 1-3: Patients receive dexamethasone IV and PO on days 1, 8, and 15, daratumumab IV on days 1, 8, and 15, and bortezomib subcutaneously (SC) on days 1, 4, 8, and 11. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity.

INDUCTION CYCLES 4-8: Patients receive dexamethasone IV and PO on days 1, 8, 15, and 22, daratumumab IV on days 1 and 15, and ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Eligible patients then undergo stem cell transplant per standard of care. Patients who have at least stable disease after induction and patients who have undergone transplant continue to Maintenance.

MAINTENANCE: Patients receive dexamethasone IV on day 1, daratumumab IV on day 1, and ixazomib PO on days 1, 8, and 15. Cycles repeat every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

Drug: Bortezomib
Given SC
Other Names:
  • MLN341
  • PS-341
  • Velcade

Biological: Daratumumab
Given IV
Other Names:
  • Anti-cluster of differentiation 38 (CD38) Monoclonal Antibody
  • Darzalex
  • HuMax-CD38

Drug: Dexamethasone
Given IV and PO
Other Names:
  • Decadron
  • Dexasone
  • Diodex
  • Hexadrol
  • Maxidex

Drug: Ixazomib
Given PO
Other Names:
  • Ninlaro
  • MLN2238




Primary Outcome Measures :
  1. ≥ Very good partial response (VGPR) response rate [ Time Frame: After cycle 8 (224 days) ]
    This will be defined as the proportion of subjects who achieved a response of VGPR or better (stringent complete response [sCR], complete response [CR], or VGPR) after induction cycle 8 treatment. Response will be determined by modified International Myeloma Working Group (IMWG) criteria.


Secondary Outcome Measures :
  1. Stem cell mobilization [ Time Frame: After cycle 3 (84 days) ]
    This will be defined as the proportion of subjects with successful stem cell mobilization after induction cycle 3. A successful stem cell mobilization is defined as the ability to collect a total of at least 2 x 10⁶ cluster of differentiation 34+ (CD34+) cells/kg.

  2. Best response on study [ Time Frame: Up to 5 years after study start ]
    Best response on study refers to the best response prior to discontinuation of all study therapy.

  3. Objective response rate (ORR) [ Time Frame: Up to 5 years after study start ]
    Objective response rate will be defined as the proportion of treated subjects who achieve a best response of CR, sCR, VGPR, or partial response (PR) using the IMWG criteria.

  4. Minimal residual disease (MRD) [ Time Frame: Up to 5 years after study start ]
    The achievement of minimal residual disease will be evaluated and reported on patients that achieve a complete response. Next-Generation sequencing will be performed to evaluate MRD.

  5. Progression-Free Survival (PFS) [ Time Frame: Up to 5 years after study start ]
    Progression-free survival (PFS) is defined as the time from first dose of study drug until documented progression or death. A subject who neither progresses nor dies will be censored on the date of his or her last tumor assessments.

  6. Time to response [ Time Frame: Up to 5 years after study start ]
    Time to response is defined as the time from first dose of study drug to the first documentation of response PR or better. This analysis will be restricted to subjects whose best response is PR or better.

  7. Duration of response (DOR) [ Time Frame: Up to 5 years after study start ]
    Duration of response is the time from first response (PR or better) until a progression event (documented progression or death). Only subjects who ever achieved a response of PR or better will be considered. Subjects who neither progress nor die will be censored on the date of their last tumor assessment.



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

Inclusion Criteria:

  • Patients must meet the following criteria on screening examination to be eligible to participate in the study. All laboratory assessments should be performed within 21 days of initiation of protocol therapy unless otherwise specified. Subject is, in the investigator's opinion, willing and able to comply with the protocol requirements
  • Subject has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Have documented multiple myeloma as defined by the International Myeloma Working Group (IMWG) 2014 criteria including: Clonal bone marrow plasma cells ≥ 10% (If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement). In addition, the patient must meet one of the criteria in d1 or d2:

    • Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following):

      • Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal (ULN) or > 2.75 mmol/L (> 11 mg/dL)
      • Renal insufficiency: Creatinine clearance (CrCl) < 40 mL/min (measured or estimated by validated equations) or serum creatinine > 177 umol/L (> 2 mg/dL)
      • Anemia: hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value < 100 g/L
      • Bone lesions: 1 or more osteolytic lesions on skeletal radiography, computed tomography (CT), or magnetic resonance imaging (MRI)

        • Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used
    • Any one or more of the following:

      • Clonal bone marrow plasma cell percentage ≥ 60%

        • Clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used
      • Involved:uninvolved serum free light chain (FLC) ratio > 100

        • These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved FLC must be ≥ 100 mg/L
      • > 1 focal lesions on MRI studies; Each focal lesion must be 5 mm or more in size
  • Measurable disease as defined by any of the following:

    • Serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours. Note: All attempts should be made to determine eligibility of the subject based on the central laboratory results of screening blood and urine M-protein measurements. In exceptional circumstances, the local laboratory results for blood and urine M-protein measurements may be used to determine eligibility, but only if the results are clearly (eg, 25% or more) above the thresholds for measurability; or
    • Immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE), or immunoglobulin M (IgM) multiple myeloma: serum M-protein level ≥ 0.5 g/dL or urine M-protein level ≥ 200 mg/24 hours; or
    • Light chain multiple myeloma without measurable disease in the urine: serum Ig FLC ≥ 10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio
  • Prior treatment to stabilize the patient with steroids up to 160 mg IV equivalents of dexamethasone is allowed
  • Prior treatment to stabilize the patient with bortezomib up to 2 doses of 1.3 mg/m² each dosing equivalent is allowed
  • Subject agrees to refrain from blood donations during therapy on study and for 8 weeks after therapy is completed
  • Female patients who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form 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 childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-International Unit (mIU)/mL within 10-14 days prior to and again within 24 hours of starting study drugs
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:

    • 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.)

Exclusion Criteria:

  • Diagnosed with smoldering multiple myeloma (MM), monoclonal gammopathy of undetermined significance, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, amyloidosis or primary or secondary plasma cell leukemia
  • Participant has ≥ grade 3 peripheral neuropathy, or grade 2 with pain on clinical examination within 21 days before initiation of protocol therapy
  • Renal insufficiency, defined as creatinine clearance ≤ 30 mL/min (either actual or calculated value), within 21 days of initiation of protocol therapy. The Cockcroft-Gault formula should be used for calculating creatinine clearance values
  • Platelet count ≤ 75,000 cells/mm³ at time of screening evaluation. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment
  • Participants with an absolute neutrophil count (ANC) ≤ 1000 cells/mm³ at time of screening evaluation. Growth factors may not be used to meet ANC eligibility criteria within 14 days of obtaining screening evaluation
  • Participants with hemoglobin level < 7.0 g/dL, at time of screening. Transfusion may not be used to meet eligibility criteria within 7 days of obtaining screening evaluation
  • Participants with hepatic impairment, defined as bilirubin ≥ 1.5 x institutional upper limit of normal (ULN) or aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]), or alkaline phosphatase ≥ 3 x institutional ULN, within 21 days of initiation of protocol therapy
  • Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. once daily (q.d.) or its equivalent) for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to study treatment.)
  • Steroids more than 160 mg IV equivalents of dexamethasone or bortezomib > 2 doses of 1.3 mg/m² each dosing equivalents
  • Known significant cardiac abnormalities including:

    • Congestive heart failure, New York Heart Association (NYHA) class III or IV
    • Uncontrolled angina, arrhythmia or hypertension
    • Myocardial infarction within the past six months
    • Any other uncontrolled or severe cardiovascular condition
    • Prior cerebrovascular event with residual neurologic deficit
  • Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal
  • Has known moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  • Serious, intercurrent illness including, but not limited to, clinically relevant active infection, uncontrolled diabetes mellitus, or serious co-morbid medical conditions such as chronic restrictive pulmonary disease, and cirrhosis
  • Seropositive for human immunodeficiency virus (HIV)
  • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR
  • Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
  • Any condition, including laboratory abnormalities, that in the opinion of the investigator places the subject at unacceptable risk if he/she were to participate in the study
  • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Known hypersensitivity to acyclovir or similar anti-viral drug
  • Known intolerance to steroid therapy
  • Participants with known central nervous system (CNS) involvement
  • Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to dexamethasone, boron or mannitol
  • Female participants pregnant or breast-feeding
  • Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of the surgery
  • Participants with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to him/her by the study staff
  • Prior exposure to anti-CD38 therapy
  • Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
  • Systemic treatment, within 14 days before the first dose of ixazomib, with strong cytochrome P450, family 3, subfamily A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • 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
  • Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not

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): NCT03942224


Contacts
Layout table for location contacts
Contact: Ajay Nooka, MD, MPH 404-778-3612 anooka@emory.edu

Locations
Layout table for location information
United States, Georgia
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Shondolyn Richburg    404-778-3612    shondolyn.k.richburg@emory.edu   
Contact: Mikayla Williams    404-778-4713    mikayla.williams@emory.edu   
Sponsors and Collaborators
Emory University
Takeda
Janssen, LP
Investigators
Layout table for investigator information
Principal Investigator: Ajay Nooka, MD, MPH Emory University

Layout table for additonal information
Responsible Party: Ajay Nooka, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03942224     History of Changes
Other Study ID Numbers: IRB00102336
NCI-2018-03615 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4547-18 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: December 4, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Daratumumab
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
Dexamethasone
Dexamethasone acetate
Bortezomib
Ixazomib
BB 1101
Antibodies, Monoclonal
Glycine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones