Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Daratumumab, Pomalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

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: NCT03841565
Recruitment Status : Not yet recruiting
First Posted : February 15, 2019
Last Update Posted : October 17, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

Brief Summary:
This phase II trial studies how well daratumumab, pomalidomide, and dexamethasone work in treating patients with multiple myeloma that has come back (relapsed). Immunotherapy with daratumumab may induce changes in body?s immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as pomalidomide and dexamethasone, 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. Giving daratumumab with dexamethasone and pomalidomide may work bettering in treating patient compared to dexamethasone and pomalidomide alone.

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

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the overall response rate (partial response [PR], very good partial response [VGPR], complete response [CR], or stringent complete response [sCR]) of daratumumab retreatment in combination with pomalidomide and dexamethasone (DPd) in patients with relapsed refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. To assess progression free survival and overall survival associated with retreatment with daratumumab in combination with pomalidomide and dexamethasone (DPd) in patients with relapsed and refractory multiple myeloma.

II. To determine the toxicities associated with retreatment with daratumumab in combination with pomalidomide and dexamethasone (DPd) .

OUTLINE:

Patients receive pomalidomide orally (PO) once daily (QD) on days 1-21 and daratumumab intravenously (IV) on days 1, 8, 15, and 22 of cycles 1-2, days 1-15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Cycles every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for every 3 months until subsequent treatment or progressive disease, then every 6 months for up to 3 years.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Daratumumab Retreatment in Patients With Relapsed Multiple Myeloma
Estimated Study Start Date : March 31, 2020
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : March 31, 2025


Arm Intervention/treatment
Experimental: Treatment (pomalidomide, daratumumab, dexamethasone)
Patients receive pomalidomide PO QD on days 1-21 and daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, days 1-15 of cycles 3-6, and day 1 of subsequent cycles. Patients also receive dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Cycles every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: Daratumumab
Given IV
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Drug: Dexamethasone
Given PO
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycadron
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • Decadron DP
  • Decalix
  • Decameth
  • Decasone R.p.
  • Dectancyl
  • Dekacort
  • Deltafluorene
  • Deronil
  • Desamethasone
  • Desameton
  • Dexa-Mamallet
  • Dexa-Rhinosan
  • Dexa-Scheroson
  • Dexa-sine
  • Dexacortal
  • Dexacortin
  • Dexafarma
  • Dexafluorene
  • Dexalocal
  • Dexamecortin
  • Dexameth
  • Dexamethasone Intensol
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • TaperDex
  • Visumetazone
  • ZoDex

Drug: Pomalidomide
Given PO
Other Names:
  • 4-Aminothalidomide
  • Actimid
  • CC-4047
  • Imnovid
  • Pomalyst




Primary Outcome Measures :
  1. Best overall response rate to the therapy [ Time Frame: Up to 3 years ]
    A success will be defined as a partial response or better noted as the objective status on two consecutive evaluations. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.


Secondary Outcome Measures :
  1. Overall survival time [ Time Frame: From registration to death due to any cause, assessed up to 3 years ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.

  2. Progression-free survival [ Time Frame: From registration to the earliest date of documentation of disease progression on initial therapy or death due to any cause, assessed up to 3 years ]
    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

  3. Incidence of adverse events [ Time Frame: Up to 3 years ]
    Will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.


Other Outcome Measures:
  1. Proportion of minimal residual disease (MRD) negativity [ Time Frame: Up to 3 years ]
    MRD will be assessed on bone marrow aspirate in all patients achieving complete response (CR) or stringent CR (sCR). The proportion of patients who achieve MRD negative status will be estimated by the number of patients who are MRD negative divided by the total number of evaluable patients who achieve CR or sCR. Exact binomial 95% confidence intervals for the true MRD negative rate will be calculated.

  2. Changes in clonal population and CD38 expression [ Time Frame: Baseline up to 3 years ]
    Will be summarized descriptively by median, min, max, and interquartile range at each time point. Changes from baseline to after treatment will be assess using paired analyses, including Wilcoxon signed rank tests.



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:

  • Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min (obtained =< 14 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1000/mm^3 (obtained =< 14 days prior to registration)
  • Untransfused platelet count >= 75,000/mm^3 (obtained =< 14 days prior to registration)
  • Hemoglobin >= 8.0 g/dL (obtained =< 14 days prior to registration)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (except for patients with Gilbert?s syndrome) (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (obtained =< 14 days prior to registration)
  • Measurable disease of multiple myeloma as defined by at least ONE of the following:

    • Serum monoclonal protein >= 1.0 g/dL
    • >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
    • Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    • Bone marrow >= 30% plasma cells
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Relapsed multiple myeloma (MM) requiring treatment who have previously received a daratumumab alone or in a daratumumab containing combination and

    • Had at least a partial response to therapy, and had disease progression on or within 60 days of discontinuation
    • At least 3 months should have elapsed since last exposure to daratumumab
    • Patients must have been previously exposed to both a proteasome inhibitor and an immunomodulatory imide drug (IMiD)

      • Examples of proteasome inhibitors:

        • Bortezomib, carfilzomib, ixazomib, marizomib, oprozomib
      • Examples of IMiD?s:

        • Thalidomide, lenalidomide, pomalidomide
  • Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
  • Willing to follow strict birth control measures

    • Female patients: If they are of childbearing potential, agree to one of the following:

      • 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, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
      • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
    • Male patients: even if surgically sterilized (i.e., 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
      • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Willing to follow the requirements of the Pomalyst Risk Evaluation and Mitigation Strategy (REMS) program
  • Willing to provide bone marrow and blood samples for planned research

Exclusion Criteria:

  • Refractory to pomalidomide
  • Concurrent amyloid light chain (AL) amyloidosis with organ involvement
  • Diagnosed or treated for another malignancy =< 2 years prior to registration or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection
  • Any of the following because this study involves an investigational agent, whose genotoxic, mutagenic and teratogenic effects, on the developing fetus and newborn are unknown:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Other concurrent chemotherapy, or any ancillary therapy considered investigational. NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
  • Major surgery =< 14 days prior to registration
  • Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction =< 6 months. Note: Prior to entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Known human immunodeficiency virus (HIV) positive
  • Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
  • 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 (i.e., 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) deoxyribonucleic acid (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 serious medical or psychiatric illness that could, in the investigator?s opinion, potentially interfere with the completion of treatment according to this protocol
  • Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or investigator's brochure) or known sensitivity to mammalian-derived products
  • Known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal
  • Known moderate or severe persistent asthma within the past 2 years or currently has uncontrolled asthma of any classification
  • Total bilirubin =< 1.5 x ULN (except for patients with Gilbert?s syndrome)

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): NCT03841565


Locations
Layout table for location information
United States, Illinois
Illinois CancerCare-Peoria Not yet recruiting
Peoria, Illinois, United States, 61615
Contact: Jennifer A. Anderson    309-243-3605    andersonj@illinoiscancercare.com   
Principal Investigator: Gregory J. Gerstner         
United States, Michigan
Michigan Cancer Research Consortium NCORP Not yet recruiting
Ann Arbor, Michigan, United States, 48106
Contact: Lauren Swafford    734-712-4329    Lauren.Swafford@stjoeshealth.org   
Principal Investigator: Christopher M. Reynolds         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Shaji K. Kumar    507-284-2511      
Principal Investigator: Shaji K. Kumar         
United States, Wisconsin
Saint Vincent Hospital Cancer Center Green Bay Not yet recruiting
Green Bay, Wisconsin, United States, 54301
Contact: Amy J. Koffarnus    920-433-8261    Amy.Koffarnus@hshs.org   
Principal Investigator: Anthony J. Jaslowski         
Aurora Cancer Care-Milwaukee West Not yet recruiting
Wauwatosa, Wisconsin, United States, 53226
Contact: Jennifer Mathieu    414-302-2312    jennifer.mathieu@aurora.org   
Principal Investigator: Michael A. Thompson         
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Shaji K Kumar Academic and Community Cancer Research United

Layout table for additonal information
Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT03841565     History of Changes
Other Study ID Numbers: ACCRU-MY-1601
NCI-2019-00386 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-MY-1601 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019

Layout table for additional information
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.: 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
Thalidomide
Dexamethasone
Dexamethasone acetate
Pomalidomide
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists