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CURATE.AI Optimized Modulation for Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03759093
Recruitment Status : Not yet recruiting
First Posted : November 29, 2018
Last Update Posted : November 29, 2018
Sponsor:
Collaborator:
National University, Singapore
Information provided by (Responsible Party):
Haematology-Oncology, National University Hospital, Singapore

Brief Summary:
Clinical trial applying CURATE.AI, a Phenotypic Precision Medicine (PPM) platform, to velcade and cyclophosphamide dosing in multiple myeloma patients to show improvement in response.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Velcade Drug: Cyclophosphamide Drug: Dexamethasone Other: CURATE.AI-Guided dosage modulation Phase 2 Phase 3

Detailed Description:
In conventional combination chemotherapy, drug doses are typically determined using dose escalation to reach a maximum tolerated dose (MTD) or via dose expansion to identify suitable regimen administration guideline, and the combinations are subsequently administered at fixed doses. During the course of treatment, the patient's response to therapy evolves and changes due to the time-dependent, dose dependent, and patient-specific nature of drug synergy and resulting efficacy and tolerability. To overcome this challenge, we have developed CURATE.AI, a Phenotypic Precision Medicine (PPM) platform, which has been clinically validated and used to prospectively optimize patient liver transplant immunosuppression, and tuberculosis therapy, among other indications. In this study, CURATE.AI may improve patient response by providing dose recommendations for velcade and cyclophosphamide to the clinical team over the course of the patient's treatment.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Phenotypic Personalized Medicine: Systematically Optimized Combination Therapy in Multiple Myeloma Using CURATE.AI
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 1, 2021
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Bortezomib

Arm Intervention/treatment
Active Comparator: Standard of Care
Dosing of velcade, cyclophosphamide and dexamethasone according to standard of care
Drug: Velcade
0.7,1.0,1.3 or 1.5 mg/m2 subcutaneous (SC) injection on Day 1, 8, 15 ,22 for cycles 1 to 4 , as determined and guided by the clinical care team and/or CURATE.AI. Standard of care is 1.3 mg/m2 SC on Day 1, 8, 15, 22 for cycles 1 to 4.
Other Name: Bortezomib

Drug: Cyclophosphamide
100, 150, 200, 250 ,300, 350 ,400 ,450 or 500 mg PO on Day 1, 8, 15, 22 for cycles 1 to 4 as determined and guided by the clinical care team and/or CURATE.AI. Standard of care is 500 mg PO on Day 1 ,8, 15, 22 for cycles 1 to 4.

Drug: Dexamethasone
8, 12 , 16, 20, 24, 28, 32 , 36 or 40 mg PO on Day 1 ,8 , 15, 22 for cycles 1 to 4, as determined and guided by the clinical care team. Standard of care is 40mg PO on Day 1, 8, 15, 22 for cycles 1 to 4.

Experimental: CURATE.AI-guided dosing
CURATE.AI optimized modulation of velcade, cyclophosphamide and dexamethasone
Drug: Velcade
0.7,1.0,1.3 or 1.5 mg/m2 subcutaneous (SC) injection on Day 1, 8, 15 ,22 for cycles 1 to 4 , as determined and guided by the clinical care team and/or CURATE.AI. Standard of care is 1.3 mg/m2 SC on Day 1, 8, 15, 22 for cycles 1 to 4.
Other Name: Bortezomib

Drug: Cyclophosphamide
100, 150, 200, 250 ,300, 350 ,400 ,450 or 500 mg PO on Day 1, 8, 15, 22 for cycles 1 to 4 as determined and guided by the clinical care team and/or CURATE.AI. Standard of care is 500 mg PO on Day 1 ,8, 15, 22 for cycles 1 to 4.

Drug: Dexamethasone
8, 12 , 16, 20, 24, 28, 32 , 36 or 40 mg PO on Day 1 ,8 , 15, 22 for cycles 1 to 4, as determined and guided by the clinical care team. Standard of care is 40mg PO on Day 1, 8, 15, 22 for cycles 1 to 4.

Other: CURATE.AI-Guided dosage modulation
CURATE.AI-guided modulation of Velcade and Cyclophosphamide dosages




Primary Outcome Measures :
  1. Response rate [ Time Frame: Up to 16 weeks or at the end of cycle 4 of treatment (each cycle is 28 days) ]
    Complete response and partial response rate at the end of cycle 4


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 16 weeks or at the end of cycle 4 of treatment (each cycle is 28 days) ]
    Occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria.



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Ages Eligible for Study:   21 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults diagnosed with multiple myeloma, with relapsing and refractory disease at study entry
  2. Patient has newly diagnosed myeloma prior to any induction treatment
  3. Patients must have evaluable multiple myeloma with at least one of the following (within 21 days of starting treatment)a. Serum M-protein = 0.5g/dL, orb. In subjects without detectable serum M-protein, Urine M-protein = 200mg/24 hour, or serum free light chai (sFLC) > 100mg/L (involved light chain) and an abnormal kappa/Lambda ratio
  4. Males and females = 21 years of age or > country's legal age for adult consent5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
  5. Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:a. Absolute neutrophil count (ANC) = 1,000/mm3 and platelet = 50,000/mm3 (= 30,000/mm3 if myeloma involvement in the bone marrow is >50%)b. Total bilirubin = 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 xULN. c. Calculated creatinine clearance = 45mL/min or creatinine < 3mg/dL.

Exclusion Criteria:

  1. Female patients who are lactating or pregnant
  2. Multiple Myeloma of immunoglobulin M subtype
  3. Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 14 days prior to informed consent obtained
  4. POEMS syndrome
  5. Plasma cell leukemia or circulating plasma cells = 2 x 109/L
  6. Waldenstrom's Macroglobulinaemia
  7. Patients with known amyloidosis
  8. Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting pomalidomide treatment
  9. Focal radiation therapy within 7 days prior to start of treatment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to start of treatment
  10. Immunotherapy (excluding steroids) 21 days prior to start of treatment
  11. Major surgery (excluding kyphoplasty) within 28 days prior to start of Treatment
  12. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischaemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 4 months prior to informed consent obtained
  13. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed)
  14. Patients with known cirrhosis
  15. Second malignancy within the past 3 years except: a. Adequately treated basal cell or squamous cell skin cancer, b. Carcinoma in situ of the cervix. Breast carcinoma in situ with full surgical resection
  16. Patients with myelodysplastic syndrome
  17. Patients with steroid or lenalidomide hypersensitivity
  18. Prior treatment with Velcade
  19. Ongoing graft-versus-host disease
  20. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to starting treatment
  21. Contraindication to any of the required concomitant drugs or supportive treatments
  22. Any clinically significant medical disease or psychiatric condition that, in the investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent.

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): NCT03759093


Contacts
Contact: Wee Joo Chng, Prof 67795555 mdccwj@nus.edu.sg
Contact: Sanjay de Mel, Dr 67795555 sanjay_widanalage@nuhs.edu.sg

Locations
Singapore
National University Hospital Not yet recruiting
Singapore, Singapore, 119228
Contact: Wee Joo Chng, Prof    67795555    mdccwj@nus.edu.sg   
Contact: Sanjay de Mel, Dr    67795555    sanjay_widanalage@nuhs.edu.sg   
Principal Investigator: Wee Joo Chng, Prof         
Sub-Investigator: Edward Chow, Dr         
Sub-Investigator: Dean Ho, Prof         
Sub-Investigator: Sanjay de Mel, Dr         
Sub-Investigator: Melissa Ooi, Dr         
Sponsors and Collaborators
National University Hospital, Singapore
National University, Singapore

Publications:
Pantuck, A.J., Lee, D.K., Kee, T., Wang, P., Lakhotia, S., Silverman, M.H., Mathis, C., Drakaki, A., Belldegrun, A.S., Ho, C.M. and Ho, D., 2018. Modulating BET Bromodomain Inhibitor ZEN‐3694 and Enzalutamide Combination Dosing in a Metastatic Prostate Cancer Patient Using CURATE. AI, an Artificial Intelligence Platform. Advanced Therapeutics, 1(6), p.1800104.

Responsible Party: Haematology-Oncology, Professor Chng Wee Joo, National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03759093     History of Changes
Other Study ID Numbers: 2015/00280
First Posted: November 29, 2018    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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 acetate
Dexamethasone
Cyclophosphamide
Bortezomib
BB 1101
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