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Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed 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: NCT04151667
Recruitment Status : Recruiting
First Posted : November 5, 2019
Last Update Posted : November 5, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Brief Summary:
This is a Phase II study of daratumumab based therapies for older adults with multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Injection Drug: Dexamethasone Oral Drug: Lenalidomide Pill Drug: Bortezomib Injection Phase 2

Detailed Description:
In this response adapted approach, older adults with newly diagnosed symptomatic multiple myeloma will receive daratumumab and dexamethasone for 2 months. Patients who achieve a partial response or better will continue on daratumumab. Patients who achieve less than a partial response will have lenalidomide or bortezomib added to their therapy. Patients who experience progressive disease on daratumumab after the initial 2 months of monotherapy or on the combination of daratumumab and either lenalidomide or bortezomib will come off study

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Daratumumab Based Response Adapted Therapy for Older Adults With Newly Diagnosed Multiple Myeloma
Actual Study Start Date : November 1, 2019
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : November 1, 2023


Arm Intervention/treatment
Experimental: A: Daratumumab & Dexamethasone
All participants will receive 1800 mg in 15 ml Daratumumab by subcutaneous injection weekly and be given 20 mg of Dexamethasone orally once a week for 2 months. Patients who receive a partial response or better will continue on this arm.
Drug: Daratumumab Injection
Patient will receive daratumumab (1800 mg in 15 ml) administered by manual subcutaneous injections weekly for the first 8 weeks, every other week for the next 16 weeks and every 4 weeks after.
Other Name: Darzalex

Drug: Dexamethasone Oral
The dexamethasone starting dose will be 20 mg PO once a week. Commercial dexamethasone will be used. Dexamethasone is often supplied in 4 mg tablets. Accordingly, patients will take 5 (4 mg tablets) one day of the week prior to the administration of daratumumab if this corresponds to a daratumumab dosing days. In non daratumumab dosing days, dexamethasone will be taken by the patient at home, usually in the morning with breakfast.
Other Name: Decadron

Experimental: B: Daratumumab, Dexamethasone and Lenalidomide
Participants who have less than a partial response to Arm A may have Lenalidomide added to their treatment. Lenalidomide will be given orally on days 1-21 of each 28 day treatment cycle.
Drug: Daratumumab Injection
Patient will receive daratumumab (1800 mg in 15 ml) administered by manual subcutaneous injections weekly for the first 8 weeks, every other week for the next 16 weeks and every 4 weeks after.
Other Name: Darzalex

Drug: Dexamethasone Oral
The dexamethasone starting dose will be 20 mg PO once a week. Commercial dexamethasone will be used. Dexamethasone is often supplied in 4 mg tablets. Accordingly, patients will take 5 (4 mg tablets) one day of the week prior to the administration of daratumumab if this corresponds to a daratumumab dosing days. In non daratumumab dosing days, dexamethasone will be taken by the patient at home, usually in the morning with breakfast.
Other Name: Decadron

Drug: Lenalidomide Pill

Lenalidomide will be given orally on days 1-21 of a 28 days cycle. The starting dose of lenalidomide will be based on the patient creatinine clearance per the package insert.

Specifically patients with a creatinine clearance ≥ 50 ml/min will receive 25 mg of lenalidomide PO Days 1-21. Patients with a creatinine clearance ≥ 30 but less than 50 ml/min will receive 10 mg of lenalidomide.

Patients with a creatinine clearance < 30 ml/min are not eligible but patients who experience a deterioration in the renal function during screening or treatment may continue on lenalidomide therapy as long as the risk / benefit profile is deemed acceptable, that study therapy is in the best interest of the patient and after discussion with the study principal investigator / sponsor.

Other Name: Revlimid

Experimental: C: Daratumumab, Dexamethasone and Bortezomib
Participants who have less than a partial response to Arm A may have Bortezomib added to their treatment. Bortezomib will be given weekly in subcutaneous injections at a starting dose of 1/3 mg/m^2 Days 1,8 and 15 of each 28 day treatment cycle.
Drug: Daratumumab Injection
Patient will receive daratumumab (1800 mg in 15 ml) administered by manual subcutaneous injections weekly for the first 8 weeks, every other week for the next 16 weeks and every 4 weeks after.
Other Name: Darzalex

Drug: Dexamethasone Oral
The dexamethasone starting dose will be 20 mg PO once a week. Commercial dexamethasone will be used. Dexamethasone is often supplied in 4 mg tablets. Accordingly, patients will take 5 (4 mg tablets) one day of the week prior to the administration of daratumumab if this corresponds to a daratumumab dosing days. In non daratumumab dosing days, dexamethasone will be taken by the patient at home, usually in the morning with breakfast.
Other Name: Decadron

Drug: Bortezomib Injection
Bortezomib will be given weekly subcutaneously in an effort to decrease the toxicity of the therapy. Specifically patients will receive a starting dose of bortezomib of 1.3 mg/m^2 Days 1,8,15 of a 28 day cycle. Bortezomib will be administered in the cancer center per standard of care procedures.
Other Name: Velcade




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Up to 8 months ]
    Overall Response Rate (partial response or better) of the response adapted strategy using the uniform response criteria of the International Myeloma Working Group (IMWG).


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 2 years ]
    Progression Free Survival (PFS) from start of treatment to death of any cause, disease progression or relapse of the date of last follow-up, whichever comes first. he PFS will be estimated by the Kaplan-Meier method and 95% confidence interval (CI) will be computed by complementary log-log transformation. The 1 and 2 year PFS and 95% Confidence Intervals will be reported.

  2. Overall Survival [ Time Frame: Up to 2 years ]
    Overall Survival (OS) from start of treatment to death of any cause or the date of last follow-up, whichever comes first. OS will be estimated by the Kaplan-Meier method and 95% confidence interval will be computed by complementary log-log transformation. The 2 year OS and 95% CI will be reported.


Other Outcome Measures:
  1. Number of Participants who Continue on Arm A after 2 cycles [ Time Frame: At the end of Cycle 2 (each cycle is 28 days) ]
    The number of participants who continue on Daratumumab and Dexamethasone after 2 cycles

  2. Number of Participants without Minimal Residual Disease [ Time Frame: Up to 8 months ]
    The number of patients who are without minimal residual disease (MRD) using Next Generation Sequencing (NGS) will be estimated and the 95% confidence interval will be computed by the Clopper-Pearson method.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Understand and voluntarily sign an informed consent form
  • Age 65 years or older and presence of coexisting conditions which in the opinion of the treating physician are likely to result in the development of unacceptable side effects associated with high-dose chemotherapy with stem-cell transplantation
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Diagnosed with multiple myeloma and be considered to have active disease with either elevated Calcium, Renal Failure, Anemia, Bone Lesions (CRAB) criteria (hypercalcemia, renal failure, anemia, or bone lesions) or myeloma defining events (bone marrow ≥ 60% plasma cells, serum free light chain (sFLC) ratio≥ 100 or MRI or Positron Emission Tomogrphy [PET] defined lesions). Patients must not have received an active chemotherapy regimen. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start. Dexamethasone up to 160 mg total dose is allowed prior to participation
  • Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL), urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100mg/L)
  • Eastern Cooperative Group (ECOG) Performance Status of 0 or 2.
  • Serum bilirubin levels </=1.5 times the upper limit of the normal range for the laboratory (ULN).
  • Serum Aspirtate Transaminase (AST) or serum Alanine Aminotransferase (ALT) levels </=2 x Upper Limit of Normal (ULN)
  • Must have adequate bone marrow function: a. Absolute neutrophil count > 1,000 cells/mm3 (1.0 x 109/L). b. Platelets >/= 75,000 /mm3.
  • Hemoglobin > 8 g/dL (transfusions are allowed)
  • Calculated creatinine clearance >/=30ml/min by Cockcroft-Gault formula.
  • Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

  • Ongoing severe infection requiring intravenous antibiotic treatment.
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years.
  • Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
  • Patients with known Chronic Obstructive Pulmonary Disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal and , moderate or severe persistent asthma within the past 2 years or uncontrolled asthma. Patients with a history of COPD will have pulmonary function testing to include FEV1
  • Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or lactating females.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known allergy or hypersensititvity or intolerance to any of the study drugs, hyaluronidase, monocolonal antibodies (mAbs), human proteins, or their excipients (refer to daratumumab IB), or known sensitivity to mammalian derived products
  • 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).

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): NCT04151667


Locations
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United States, Florida
H. Lee Moffitt Cancer & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Anna Niebrzydowski    813-745-3304    Anna.Niebrzydowski@Moffitt.org   
Principal Investigator: Rachid C Baz, MD         
Sub-Investigator: Melissa Alsina, MD         
Sub-Investigator: Brandon J Blue, MD         
Sub-Investigator: Jason B Brayer, MD, PhD         
Sub-Investigator: Kenneth H Shain, MD, PhD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Rachid C Baz, MD H. Lee Moffitt Cancer & Research Institute
Additional Information:
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Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT04151667    
Other Study ID Numbers: MCC-20130
First Posted: November 5, 2019    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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 H. Lee Moffitt Cancer Center and Research Institute:
myeloma
daratumumab
Additional relevant MeSH terms:
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Multiple Myeloma
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
Lenalidomide
Bortezomib
Daratumumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors