CURATE.AI Optimized Modulation for Multiple Myeloma

Sponsor

National University Hospital, Singapore (Other)

Overall Status

Unknown status

CT.gov ID

NCT03759093

Collaborator

National University, Singapore (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Clinical trial applying CURATE.AI, a Phenotypic Precision Medicine (PPM) platform, to Bortezomib, Thalidomide and Cyclophosphamide dosing in multiple myeloma patients to show improvement in response.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bortezomib Drug: Cyclophosphamide Drug: Dexamethasone Other: CURATE.AI-Guided dosage modulation Drug: Thalidomide Drug: Bortezomib Drug: Cyclophosphamide Drug: Thalidomide Drug: Dexamethasone	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 Bortezomib, Thalidomide and Cyclophosphamide to the clinical team over the course of the patient's treatment.

Study Design

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

Mar 1, 2022

Anticipated Study Completion Date :

Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard of Care Dosing of VCD(bortezomib, cyclophosphamide, dexamethasone) or VTD (bortezomib, thalidomide, dexamethasone) combinations according to standard of care	Drug: Bortezomib Dose in the range of 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 by the clinical care team according to standard of care Other Names: Velcade Drug: Cyclophosphamide Dose in range of 100, 150, 200, 250, 300, 350, 400, 450 or 500 mg per os (PO) on Day 1, 8, 15, 22 for cycles 1 to 4 as determined and guided by the clinical care team according to standard of care 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 according to standard of care Drug: Thalidomide Dose in a range of 50, 100, 150, 200 mg PO on day 1-28 for cycles 1 to 4 as determined and guided by CURATE.AI and approved by the clinical care team.
Experimental: CURATE.AI-guided dosing CURATE.AI optimized modulation of bortezomib and cyclophosphamide dosages in the VCD (bortezomib, cyclophosphamide, dexamethasone) or bortezomib and thalidomide in the VTD (bortezomib, thalidomide, dexamethasone) combinations	Other: CURATE.AI-Guided dosage modulation CURATE.AI-guided modulation of Velcade and Cyclophosphamide dosages Drug: Bortezomib Dose in a range of 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 CURATE.AI and approved by the clinical care team Other Names: Velcade Drug: Cyclophosphamide Dosing in a range of 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 CURATE.AI and approved by the clinical care team. Drug: Thalidomide Dose in a range of 50, 100, 150, 200 mg PO on day 1-28 for cycles 1 to 4 as determined and guided by CURATE.AI and approved by the clinical care team. 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 according to standard of care

Arm

Intervention/Treatment

Active Comparator: Standard of Care

Dosing of VCD(bortezomib, cyclophosphamide, dexamethasone) or VTD (bortezomib, thalidomide, dexamethasone) combinations according to standard of care

Drug: Bortezomib

Dose in the range of 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 by the clinical care team according to standard of care

Other Names:

Velcade

Drug: Cyclophosphamide

Dose in range of 100, 150, 200, 250, 300, 350, 400, 450 or 500 mg per os (PO) on Day 1, 8, 15, 22 for cycles 1 to 4 as determined and guided by the clinical care team according to standard of care

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 according to standard of care

Drug: Thalidomide

Dose in a range of 50, 100, 150, 200 mg PO on day 1-28 for cycles 1 to 4 as determined and guided by CURATE.AI and approved by the clinical care team.

Experimental: CURATE.AI-guided dosing

CURATE.AI optimized modulation of bortezomib and cyclophosphamide dosages in the VCD (bortezomib, cyclophosphamide, dexamethasone) or bortezomib and thalidomide in the VTD (bortezomib, thalidomide, dexamethasone) combinations

Other: CURATE.AI-Guided dosage modulation

CURATE.AI-guided modulation of Velcade and Cyclophosphamide dosages

Drug: Bortezomib

Dose in a range of 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 CURATE.AI and approved by the clinical care team

Other Names:

Velcade

Drug: Cyclophosphamide

Dosing in a range of 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 CURATE.AI and approved by the clinical care team.

Drug: Thalidomide

Dose in a range of 50, 100, 150, 200 mg PO on day 1-28 for cycles 1 to 4 as determined and guided by CURATE.AI and approved by the clinical care team.

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 according to standard of care

Outcome Measures

Primary Outcome Measures

Response rate [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

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults diagnosed with multiple myeloma diagnosed according to standard criteria, without prior anti-myeloma treatment at study entry
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,or
1. 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
Males and females = 21 years of age or > country's legal age for adult Consent
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2
Patients must meet the following clinical laboratory criteria with 21 days of starting treatment:
Absolute neutrophil count (ANC) = 1,000/mm3 and platelet = 50,000/mm3 (= 30,000/mm3 if myeloma involvement in the bone marrow is >50%)
Total bilirubin = 1.5 x the upper limit of the normal range (ULN). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST = 3 xULN.
Calculated creatinine clearance = 45mL/min or creatinine < 3mg/dL.
Written informed consent in accordance with federal, local and institutional guidelines

Exclusion Criteria:

Female patients who are lactating or pregnant
Multiple Myeloma of immunoglobulin M subtype
Glucocorticoid therapy (prednisolone > 30mg/day or equivalent) within 14 days prior to informed consent obtained
POEMS syndrome
Plasma cell leukemia or circulating plasma cells = 2 x 109/L
Waldenstrom's Macroglobulinaemia
Patients with known amyloidosis
Chemotherapy with approved or investigation anticancer therapeutics within 21 days prior to starting pomalidomide treatment
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
Immunotherapy (excluding steroids) 21 days prior to start of treatment
Major surgery (excluding kyphoplasty) within 28 days prior to start of treatment
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
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)
Patients with known cirrhosis
Second malignancy within the past 3 years except:
Adequately treated basal cell or squamous cell skin cancer,
Carcinoma in situ of the cervix.
Breast carcinoma in situ with full surgical resection
Patients with myelodysplastic syndrome
Patients with steroid, bortezomib, cyclophosphamide or thalidomide hypersensitivity
Prior treatment with Bortezomib
Ongoing graft-versus-host disease
Patients with pleural effusions requiring thoracentesis or ascites requiring aracentesis within 14 days prior to starting treatment
Contraindication to any of the required concomitant drugs or supportive treatments
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.