CarBiRD: Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Multiple Myeloma

• Sponsor: Weill Medical College of Cornell University (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01559935
• Collaborator: Onyx Therapeutics, Inc. (Industry)
• Enrollment: 74
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 132
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of an investigational new drug called carfilzomib, in combination with dexamethasone in subjects with newly diagnosed multiple myeloma followed by treatment with a combination of drugs clarithromycin (Biaxin®), lenalidomide (Revlimid®) and dexamethasone (Decadron®) [BiRD] then lenalidomide alone.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: carfilzomib; Drug: Dexamethasone; Drug: Clarithromycin; Drug: Lenalidomide; Drug: Dexamethasone; Drug: Lenalidomide	Phase 2

Detailed Description

While new anti-myeloma therapies such as bortezomib and immunomodulatory drugs have been developed, multiple myeloma remains an incurable malignancy. Given that obtaining a complete remission (CR) with therapy will allow patients with newly diagnosed multiple myeloma to enjoy a higher quality of life and longer duration of freedom from disease symptoms, finding an optimally effective and well-tolerated regimen is imperative.

The robust overall response rate of 91% with the BiRD regimen for patients with newly diagnosed multiple myeloma is encouraging and we believe that by adding carfilzomib the overall response rate and CR rate can be improved. As carfilzomib has proven efficacy in myeloma and in patient's who have relapsed on bortezomib, we anticipate that it will synergize with the previous BiRD regimen to induce greater reduction of tumor burden overall.

The primary endpoints include best response rate, toxicities, progression free survival, event free survival, and overall survival. In those patients who are eligible for autologous stem cell transplantation, we will also study the effect of carfilzomib on CD 34+ stem cell yield following mobilization.

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Sequential Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Newly Diagnosed Multiple Myeloma
• Actual Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Jun 7, 2016
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Car-BiRD Therapy Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD]

Drug: carfilzomib; 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles.; Drug: Dexamethasone; 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib.; Other Names: DECADRON® ; Drug: Clarithromycin; 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; Other Names: Biaxin ; Drug: Lenalidomide; 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; Other Names: Revlimid ; Drug: Dexamethasone; 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.; Drug: Lenalidomide; 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.; Other Names: Revlimid

Outcome Measures

Primary Outcome Measures

1. Response to Car-BiRD Treatment. [From baseline to best response, up to 116 weeks.]

   The best response for all patients who had at least one dose of drug was measured. Response categories: Stringent Complete Response (sCR), Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Progressive Disease (PD), Stable Disease (SD). The response is evaluated based on the IMWG criteria.

Secondary Outcome Measures

1. Event Free Survival [From date of study enrollment until the date of removal of study due to progression of disease, toxicity or withdrawal of consent, up to 1222 days.]

   an event is defined by coming off protocol for any reason, including progression of disease, lack of disease response, regimen intolerability, withdrawal of consent or death.

2. MRD Negativity Following CarBiRD Regimen [From start of study up to Revlimid Maintenance Cycle 4.]

   Minimal Residual Disease (MRD) was assessed for all participants as soon as they achieved CR/sCR, regardless of what phase they were on. MRD negativity is defined as the complete absence of plasma cells on bone marrow biopsy. MRD positivity is defined as the presence of residual plasma cells (<5%) on bone marrow biopsy. The IMWG criteria were used to determine CR and sCR.

3. Progression Free Survival [From start of study drug until first incidence of progression, up to 1222 days.]

   Progression was defined using the IMWG criteria.

4. Stem Cells Collection [At the end of the Car Phase, prior to the start of the BiRD Phase, on average after 162 days.]

   At the end of the Car Phase, all participants underwent stem cell collection.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject must voluntarily sign and understand written informed consent.

• Subject is ≥ 18 years at the time of signing the consent form.

• Subject has histologically confirmed multiple myeloma that has never before been treated.

• Subject had no anti-myeloma therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression.

• Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, > 10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, > 0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI.

• Subject has a Karnofsky performance status ≥ 60% (> 50% if due to bony involvement of myeloma (see Appendix VI).

• Subject is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin).

• Subject is registered into the mandatory RevAssist® program, and is willing and able to comply with the requirements of RevAssist® program.

• If subject is a female of childbearing potential (FCBP),† she must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.

• Subjects must meet the following laboratory parameters:

• Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L)

• Hemoglobin ≥ 7 g/dL

• Platelet count ≥ 30,000/mm3 (75 x 109/L)

• Serum SGOT/AST < 3.0 x upper limits of normal (ULN)

• Serum SGPT/ALT < 3.0 x upper limits of normal (ULN)

• Serum creatinine < 2.5 mg/dL (221 µmol/L)

• Serum total bilirubin < 2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

• Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning).

• Subject has a prior history of other malignancies unless disease free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels.

• Subject has had myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

• Female subject who is pregnant or lactating.

• Subject has known HIV infection

• Subject has known active hepatitis B or hepatitis C infection.

• Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.

• Subject has known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, thalidomide, allopurinol, or carfilzomib.

• Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment.

• Subject has any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Cornell Medical College	New York	New York	United States	10021

Sponsors and Collaborators

• Weill Medical College of Cornell University
• Onyx Therapeutics, Inc.

Investigators

• Principal Investigator: Adriana Rossi, M.D., Weill Medical College of Cornell University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Weill Medical College of Cornell University
• ClinicalTrials.gov Identifier: NCT01559935
• Other Study ID Numbers: 1108011903
• First Posted: Mar 21, 2012
• Last Update Posted: May 5, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Weill Medical College of Cornell University: Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Clarithromycin; Dexamethasone; Dexamethasone acetate; Lenalidomide; BB 1101

Study Results

Participant Flow

Pre-assignment Detail	Two subjects were ineligible and therefore never started treatment.

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Period Title: Car Phase
STARTED	72
COMPLETED	58
NOT COMPLETED	14
Period Title: Car Phase
STARTED	58
COMPLETED	54
NOT COMPLETED	4
Period Title: Car Phase
STARTED	54
COMPLETED	0
NOT COMPLETED	54

Baseline Characteristics

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Overall Participants	72
Age, Customized (years) [Mean (Full Range) ]
Car Phase	60.4
BiRD Phase	59.6
Maintenance Phase	59.2
Sex: Female, Male (Count of Participants)
Female	29 40.3%
Male	43 59.7%
Female	26 36.1%
Male	32 44.4%
Female	23 31.9%
Male	31 43.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 4.2%
Not Hispanic or Latino	61 84.7%
Unknown or Not Reported	8 11.1%
Hispanic or Latino	3 4.2%
Not Hispanic or Latino	48 66.7%
Unknown or Not Reported	7 9.7%
Hispanic or Latino	2 2.8%
Not Hispanic or Latino	45 62.5%
Unknown or Not Reported	7 9.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 6.9%
White	29 40.3%
More than one race	6 8.3%
Unknown or Not Reported	32 44.4%
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 5.6%
White	22 30.6%
More than one race	5 6.9%
Unknown or Not Reported	27 37.5%
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 4.2%
White	20 27.8%
More than one race	5 6.9%
Unknown or Not Reported	26 36.1%

Outcome Measures

1. Primary Outcome

Title	Response to Car-BiRD Treatment.
Description	The best response for all patients who had at least one dose of drug was measured. Response categories: Stringent Complete Response (sCR), Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Progressive Disease (PD), Stable Disease (SD). The response is evaluated based on the IMWG criteria.
Time Frame	From baseline to best response, up to 116 weeks.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Measure Participants	72
sCR/CR	28 38.9%
VGPR	31 43.1%
PR	11 15.3%
SD	1 1.4%
PD	0 0%
Not Evaluable	1 1.4%

2. Secondary Outcome

Title	Event Free Survival
Description	an event is defined by coming off protocol for any reason, including progression of disease, lack of disease response, regimen intolerability, withdrawal of consent or death.
Time Frame	From date of study enrollment until the date of removal of study due to progression of disease, toxicity or withdrawal of consent, up to 1222 days.

Outcome Measure Data

Analysis Population Description

44 participants analyzed out of the 72 participants initially enrolled in the study. 28 participants are active and therefore have not experienced any events leading to removal from study.

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Measure Participants	44
Median (Full Range) [Days]	401.5

3. Secondary Outcome

Title	MRD Negativity Following CarBiRD Regimen
Description	Minimal Residual Disease (MRD) was assessed for all participants as soon as they achieved CR/sCR, regardless of what phase they were on. MRD negativity is defined as the complete absence of plasma cells on bone marrow biopsy. MRD positivity is defined as the presence of residual plasma cells (<5%) on bone marrow biopsy. The IMWG criteria were used to determine CR and sCR.
Time Frame	From start of study up to Revlimid Maintenance Cycle 4.

Outcome Measure Data

Analysis Population Description

28 participants achieved CR or sCR.

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Measure Participants	28
MRD positive	10 13.9%
MRD negative	17 23.6%
Not Evaluable	1 1.4%

4. Secondary Outcome

Title	Progression Free Survival
Description	Progression was defined using the IMWG criteria.
Time Frame	From start of study drug until first incidence of progression, up to 1222 days.

Outcome Measure Data

Analysis Population Description

21 participants had an incidence of progression.

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Measure Participants	21
Median (Full Range) [months]	18.3

5. Secondary Outcome

Title	Stem Cells Collection
Description	At the end of the Car Phase, all participants underwent stem cell collection.
Time Frame	At the end of the Car Phase, prior to the start of the BiRD Phase, on average after 162 days.

Outcome Measure Data

Analysis Population Description

58 participants reached the end of the Car Phase. From those 58 participants, 52 were collected, 5 participants declined stem cell collection and 1 participant's results were not evaluable.

Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Measure Participants	52
Mean (Standard Deviation) [Number of stem cells collected per Kg]	12854635 (5388946.9)

Adverse Events

Adverse Event Reporting Description	Collection of adverse events is ongoing as 28 participants are still on trial. For the Car Phase, every adverse event not present at baseline was reported. For the BiRD and Maintenance phases, adverse events were only reported if it was a new occurrence (not present in the previous phase) or if the grade of the event increased. Grading was done using the CTCAE 4.0.
Arm/Group Title	Car-BiRD Therapy
Arm/Group Description	Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Car Phase: carfilzomib: 45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles. Dexamethasone: 20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib. BiRD Phase: Clarithromycin: 500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Lenalidomide: 25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Dexamethasone: 40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed. Maintenance Phase: Lenalidomide: 10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
All Cause Mortality
	Car-BiRD Therapy
	Affected / at Risk (%)	# Events
Total	1/72 (1.4%)
Serious Adverse Events
	Car-BiRD Therapy
	Affected / at Risk (%)	# Events
Total	26/72 (36.1%)
Cardiac disorders
atrial fibrilation	1/72 (1.4%)	1
massive heart attack	1/72 (1.4%)	1
acute coronary syndrome	1/58 (1.7%)	1
cardiac chest pain	1/54 (1.9%)	1
Gastrointestinal disorders
diarrhea	1/54 (1.9%)	2
Infections and infestations
abnominal infection	1/72 (1.4%)	2
lung infection	3/72 (4.2%)	4
URI	2/72 (2.8%)	2
UTI	2/72 (2.8%)	2
lung infection	3/58 (5.2%)	3
lung infection	4/54 (7.4%)	4
acute kidney infection	1/54 (1.9%)	1
enterocolitis infection	1/54 (1.9%)	1
Injury, poisoning and procedural complications
fall	1/72 (1.4%)	1
Metabolism and nutrition disorders
increased creatinine	1/72 (1.4%)	1
dehydration	1/72 (1.4%)	1
creatinine increase	1/54 (1.9%)	1
Musculoskeletal and connective tissue disorders
femur fracture	1/72 (1.4%)	1
spinal fracture	1/72 (1.4%)	1
back pain	1/72 (1.4%)	1
non-cardiac chest pain	1/58 (1.7%)	1
abdominal pain (small intestinal obstruction)	1/58 (1.7%)	1
non-cardiac chest pain	3/54 (5.6%)	3
spinal cord compression	1/54 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
thyroid cancer	1/72 (1.4%)	1
secondary malignancy	1/54 (1.9%)	1
Nervous system disorders
syncope	1/72 (1.4%)	1
confusion	1/72 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
dyspnea	2/72 (2.8%)	2
pulmonary embolism	1/72 (1.4%)	1
Surgical and medical procedures
surgical procedure	1/72 (1.4%)	1
Vascular disorders
fever	2/72 (2.8%)	3
thromboembolic event	1/54 (1.9%)	1
Other (Not Including Serious) Adverse Events
	Car-BiRD Therapy
	Affected / at Risk (%)	# Events
Total	72/72 (100%)
Blood and lymphatic system disorders
anemia	52/72 (72.2%)
thrombocytopenia	64/72 (88.9%)
neutropenia	13/72 (18.1%)
leukopenia	25/72 (34.7%)
lymphopenia	69/72 (95.8%)
neutropenia	6/58 (10.3%)
leukopenia	5/58 (8.6%)
lymphopenia	5/58 (8.6%)
thrombocytopenia	3/54 (5.6%)
neutropenia	18/54 (33.3%)
leukopenia	11/54 (20.4%)
Cardiac disorders
high BNP	10/72 (13.9%)
bradycardia	5/54 (9.3%)
Eye disorders
blurry vision	5/54 (9.3%)
Gastrointestinal disorders
dyspepsia	13/72 (18.1%)
constipation	18/72 (25%)
nausea	17/72 (23.6%)
anorexia	6/72 (8.3%)
diarhhea	25/72 (34.7%)
vomiting	8/72 (11.1%)
flatulance	7/72 (9.7%)
dyspepsia	4/58 (6.9%)
constipation	15/58 (25.9%)
nausea	7/58 (12.1%)
anorexia	4/58 (6.9%)
diarhhea	4/58 (6.9%)
vomiting	3/58 (5.2%)
dry mouth	4/58 (6.9%)
flatulance	3/58 (5.2%)
dyspepsia	13/54 (24.1%)
constipation	5/54 (9.3%)
nausea	4/54 (7.4%)
diarhhea	20/54 (37%)
vomiting	7/54 (13%)
dry mouth	3/54 (5.6%)
flatulance	3/54 (5.6%)
General disorders
insomnia	27/72 (37.5%)
fatigue	22/72 (30.6%)
chills	4/72 (5.6%)
insomnia	5/58 (8.6%)
malaise	3/58 (5.2%)
fatigue	9/58 (15.5%)
fatigue	5/54 (9.3%)
gait disturbance	4/54 (7.4%)
hair loss	4/54 (7.4%)
Infections and infestations
URI	12/72 (16.7%)
UTI	5/72 (6.9%)
Skin Infection	4/72 (5.6%)
URI	22/54 (40.7%)
skin Infection	4/54 (7.4%)
ear infection	3/54 (5.6%)
Injury, poisoning and procedural complications
fall	4/54 (7.4%)
Metabolism and nutrition disorders
hypocalcemia	56/72 (77.8%)
hyponatremia	42/72 (58.3%)
hypoglycemia	21/72 (29.2%)
hyperglycemia	63/72 (87.5%)
hypophosphatemia	35/72 (48.6%)
hyperkalemia	20/72 (27.8%)
hypokalemia	4/72 (5.6%)
hypomagnesemia	14/72 (19.4%)
hypermagnesemia	10/72 (13.9%)
hypoalbuminemia	39/72 (54.2%)
hyperbilirubinemia	23/72 (31.9%)
hyperuricemia	5/72 (6.9%)
hyperhidrosis	8/72 (11.1%)
elevated ALT	26/72 (36.1%)
elevated AST	30/72 (41.7%)
elevated alkaline phosphatase	34/72 (47.2%)
increased creatinine	35/72 (48.6%)
hypocalcemia	6/58 (10.3%)
hypoglycemia	14/58 (24.1%)
hypokalemia	4/58 (6.9%)
hypomagnesemia	7/58 (12.1%)
elevated ALT	3/58 (5.2%)
ALK increase	6/58 (10.3%)
increased creatinine	4/58 (6.9%)
hypocalcemia	7/54 (13%)
hypercalcemia	3/54 (5.6%)
hypoglycemia	7/54 (13%)
hypophosphatemia	5/54 (9.3%)
hypokalemia	4/54 (7.4%)
hypomagnesemia	13/54 (24.1%)
hypoalbuminemia	8/54 (14.8%)
hyperbilirubinemia	5/54 (9.3%)
hyponatremia	3/54 (5.6%)
hypernatremia	5/54 (9.3%)
elevated ALT	5/54 (9.3%)
elevated AST	4/54 (7.4%)
increased creatinine	7/54 (13%)
Musculoskeletal and connective tissue disorders
muscle spasms/cramps	13/72 (18.1%)
muscle weakness	6/72 (8.3%)
pain in legs	8/72 (11.1%)
hip pain	7/72 (9.7%)
back pain	17/72 (23.6%)
knee pain	4/72 (5.6%)
lower extremity pain	4/72 (5.6%)
muscle spasms/cramps	6/58 (10.3%)
hip pain	3/58 (5.2%)
bone pain	3/58 (5.2%)
muscle spasms/cramps	5/54 (9.3%)
shoulder pain	5/54 (9.3%)
rib pain	6/54 (11.1%)
chest pain (muscular)	4/54 (7.4%)
pain in legs	5/54 (9.3%)
hip pain	10/54 (18.5%)
back pain	8/54 (14.8%)
arthralgias	11/54 (20.4%)
neck pain	3/54 (5.6%)
pain in foot	3/54 (5.6%)
lower extremity pain	6/54 (11.1%)
upper extremity pain	6/54 (11.1%)
knee pain	3/54 (5.6%)
Nervous system disorders
peripheral neuropathy	12/72 (16.7%)
tremor	10/72 (13.9%)
anxiety/stress	13/72 (18.1%)
dizziness / lightheaded	9/72 (12.5%)
paresthesias	4/72 (5.6%)
forgetful	4/72 (5.6%)
dysgeusia	4/72 (5.6%)
headache	12/72 (16.7%)
irritability	5/72 (6.9%)
agitation	4/72 (5.6%)
concentration impairment	7/72 (9.7%)
peripheral neuropathy	3/58 (5.2%)
tremor	11/58 (19%)
dizziness / lightheaded	5/58 (8.6%)
parethesias	4/58 (6.9%)
dysgeusia	17/58 (29.3%)
irritability	7/58 (12.1%)
peripheral neuropathy	7/54 (13%)
dizziness / lightheaded	5/54 (9.3%)
headache	3/54 (5.6%)
Psychiatric disorders
depression	6/72 (8.3%)
anxiety/stress	3/54 (5.6%)
depression	5/54 (9.3%)
Renal and urinary disorders
low eGFR	37/72 (51.4%)
genitourinary frequency	4/72 (5.6%)
low eGFR	4/58 (6.9%)
genitourinary frequency	3/54 (5.6%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	11/72 (15.3%)
cough	12/72 (16.7%)
sinus congestion	10/72 (13.9%)
sore throat	4/72 (5.6%)
dyspnea	3/58 (5.2%)
lung infection	3/58 (5.2%)
cough	3/58 (5.2%)
sinus congestion	3/58 (5.2%)
lung infection	3/54 (5.6%)
cough	13/54 (24.1%)
sore throat	3/54 (5.6%)
sinus congestion	9/54 (16.7%)
allergic rhinitis	7/54 (13%)
Skin and subcutaneous tissue disorders
rash	7/72 (9.7%)
rash	13/58 (22.4%)
pruritus	3/58 (5.2%)
rash	10/54 (18.5%)
skin darknening	5/54 (9.3%)
pruritus	4/54 (7.4%)
dry skin	7/54 (13%)
Vascular disorders
edema	14/72 (19.4%)
hypertension	4/72 (5.6%)
fever	14/72 (19.4%)
edema	10/58 (17.2%)
cushingoid appearance	3/58 (5.2%)
edema	14/54 (25.9%)
hypertension	5/54 (9.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.