Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Daratumumab After Stem Cell Transplant in Treating Patients With 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: NCT03346135
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : September 2, 2019
Sponsor:
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
City of Hope Medical Center

Brief Summary:
This phase II trial studies how well daratumumab after a stem cell transplant works in treating patients with multiple myeloma. Monoclonal antibodies, such as daratumumab, may kill cancer cells that are left after chemotherapy.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Secondary Amyloidosis Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Melphalan Biological: Daratumumab Other: Laboratory Biomarker Analysis Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label, Single Arm, Phase II Study of Daratumumab as Consolidation/Maintenance Therapy After Autologous Stem Cell Transplantation in Patients With Multiple Myeloma
Estimated Study Start Date : November 17, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Treatment (ASCT, melphalan, daratumumab)
Patients undergo standard of care ASCT with a conditioning regimen of melphalan. Beginning 60-120 days after ASCT, patients receive daratumumab IV every week for 8 weeks, every 2 weeks for 16 weeks, and then every 4 weeks for up to 24 months in the absence of disease progression or unacceptable toxicity.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo standard of care ASCT with a conditioning regimen of melphalan
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • Autologous Stem Cell Transplantation

Drug: Melphalan
Undergo standard of care ASCT with a conditioning regimen of melphalan
Other Names:
  • 148-82-3
  • 241286
  • 4-[bis(2-chloroethyl)amino]-L-phenylalanine
  • 8806
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine mustard
  • L-Sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • Melphalanum
  • p-di(chloroethyl)amino-L-phenylalanine
  • Phenylalanine Mustard
  • Phenylalanine Nitrogen Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Biological: Daratumumab
Given IV
Other Names:
  • 945721-28-8
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: From date of first dose of study drug to first documented date of disease relapse, progression, or death (from any cause), whichever occurs first, assessed for up to 18 months after last dose of study drug ]
    Will be estimated using the product-limit method of Kaplan-Meier.


Secondary Outcome Measures :
  1. Minimal residual disease (MRD) defined as if a positive result is obtained using the Adaptive MRD testing [ Time Frame: Up to 30 days after last dose of study drug ]
  2. Incidence of adverse events graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 30 days after last dose of study drug ]
  3. Overall response rate (stringent complete response [sCR]/complete response [CR], very good partial response [VGPR]) based on the International Myeloma Working Group (IMWG) Uniform Response Criteria [ Time Frame: At 1 year ]
    Will be calculated as the percent of evaluable patients that have confirmed sCR/CR/VGPR (overall) or sCR/CR/VGPR/partial response (PR)/minimal response (MR) or stable disease (SD) (clinical benefit). Exact 95% confidence intervals will be calculated for these estimates. Will also be evaluated based on the number and type of prior therapy(ies).

  4. Response duration [ Time Frame: From the date of first documented response (sCR/CR/VGPR) to documented disease relapse, progression, or death, whichever occurs first, assessed up to 18 months after last dose of study drug ]
  5. Depth of response [ Time Frame: Up to 18 months after last dose of study drug ]
    Will be calculated as the percent of evaluable patients that have confirmed sCR/CR/VGPR (overall) or sCR/CR/VGPR/PR/MR or SD (clinical benefit). Exact 95% confidence intervals will be calculated for these estimates.

  6. Clinical benefit response based on the IMWG criteria [ Time Frame: Up to 18 months after last dose of study drug ]
    Will be calculated as the number of responders plus those with a PR, MR, or SD, divided by the number of evaluable patients. Exact 95% confidence intervals will be calculated for these estimates.

  7. Overall survival [ Time Frame: From date of first dose of study drug to date of death from any cause, assessed for up to 18 months after last dose of study drug ]
    Will be estimated using the product-limit method of Kaplan-Meier.



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 to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • All subjects must have the ability to understand and the willingness to sign a written informed consent
  • Histologically confirmed diagnosis of multiple myeloma; (patients with multiple myeloma with secondary amyloidosis are eligible)
  • Received at least two cycles of any regimen as initial systemic therapy for multiple myeloma and are within 2-13 months of the first dose of initial therapy
  • Eastern Cooperative Oncology Group (ECOG) =< 2
  • Patients with planned standard of care ASCT using melphalan 200 mg/m^2
  • Adequate organ function for high dose chemotherapy and autologous stem cell transplant (as per institution standard operating procedure [SOP])
  • Adequate cell dose > 2.5x10^6 CD34+ cells/kg
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Platelet count >= 75 mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • Calculated creatinine clearance >= 30 mL/min
  • Woman of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected, or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods; condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization; true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (6 months after the last dose of daratumumab for women)

    • A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 6 months after receiving the last dose of study drug

Exclusion Criteria:

  • Prior daratumumab or other anti-CD38 antibody
  • History of organ or previous autologous/allogeneic stem cell transplantation
  • Any condition medical or psychosocial that in the opinion of the investigator would hinder compliance
  • Female patients who are lactating or have a positive pregnancy test during the screening period
  • Evidence of multiple myeloma (MM) disease progression any time prior to enrollment; progression from smoldering to active myeloma is not exclusionary
  • History of plasma cell leukemia or central nervous system (CNS) involvement
  • Major surgery within 14 days prior to start of study treatment
  • Infection requiring systemic antibiotic therapy within 14 days prior to the start of study treatment
  • Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment; Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable
  • Vaccination with live attenuated vaccines within 4 weeks of first study agent administration
  • Subject is currently using or has used immunosuppressive medication within 14 days prior to the first dose of study treatment; the following are exceptions:

    • Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
    • Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
    • Steroids as premedication for hypersensitivity reaction (e.g., infusion-related reactions, computed tomography [CT] scan premedication)
  • Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis
  • Subjects with uncontrolled, systematic infection should be excluded
  • Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% predicted normal; Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV < 50%
  • Subject has known moderate or severe persistent asthma within 2 years, or currently has uncontrolled asthma of any classification; (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study)
  • Subject has active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., Crohns disease], diverticulitis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia gravis; Grave's disease; rheumatoid arthritis; hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment; the following are exceptions:

    • Subjects with vitiligo or alopecia
    • Subjects with hypothyroidism (e.g., following Hashimoto's disease) stable on hormone replacement
    • Psoriasis not requiring systemic treatment
  • Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients
  • Subject has history of primary immunodeficiency
  • Subject is positive for human immunodeficiency virus (HIV-1) chronic or active hepatitis B, or active hepatitis A or C
  • Subject has any one of the following:

    • Clinically significant abnormal electrocardiogram (ECG) finding at screening
    • Congestive heart failure (New York Heart Association class III or IV)
    • Myocardial infarction within 12 months prior to starting study treatment
    • Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
  • Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for >= 5 years with the exception of the following malignancies:

    • Basal cell carcinoma of the skin
    • Squamous cell carcinoma of the skin
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the breast
    • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system) or prostate cancer that is curative
  • Any other condition that would, in the opinion of the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

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): NCT03346135


Contacts
Layout table for location contacts
Contact: Amrita Krishnan, MD 626 256-4673 akrishnan@coh.org

Locations
Layout table for location information
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Amrita Krishnan, MD    626-256-4673    akrishnan@coh.org   
Principal Investigator: Amrita Krishnan, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Shaji Kumar, MD    507-284-2511    Kumar.Shaji@mayo.edu   
Principal Investigator: Shaji Kumar, MD         
United States, North Carolina
Levine Cancer Institute/Carolinas Health Care System Not yet recruiting
Charlotte, North Carolina, United States, 28204
Contact: Saad Usmani, MD       saad.usmani@carolinashealthcare.org   
Principal Investigator: Saad Usmani, MD         
Sponsors and Collaborators
City of Hope Medical Center
Janssen, LP
Investigators
Layout table for investigator information
Principal Investigator: Amrita Krishnan, MD City of Hope Medical Center

Layout table for additonal information
Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT03346135     History of Changes
Other Study ID Numbers: 18560
NCI-2017-02087 ( Registry Identifier: NCI CTRP )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: August 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
Neoplasms, Plasma Cell
Amyloidosis
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
Proteostasis Deficiencies
Metabolic Diseases
Melphalan
Mechlorethamine
Nitrogen Mustard Compounds
Daratumumab
Antibodies, Monoclonal
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs