Trial Outcomes & Findings for Phase II Study of Thalidomide, Clarithromycin, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma (NCT NCT00538733)

Last Updated: 2021-05-24

Results Overview

Objective response rate, defined according to the International Myeloma Working Group (IMWG) criteria as greater then or equal to a Partial Response (PR). The best response was recorded. The IMWG criteria can be found here: imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

This was collected from patients for their duration on study treatment. Only the best response was recorded. Best responses were reported at any point of the study, from start of treatment up until removal of study, which occurred up to 57.4 cycles

Results posted on

2021-05-24

Participant Flow

Participant milestones

Participant milestones
Measure	T-BiRD Therapy (All Patients) 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant).
Overall Study STARTED	26
Overall Study Removed Due to Progression of Disease	1
Overall Study Removed to Pursue a Stem Cell Transplant	11
Overall Study Removed to Pursue Alternative Theray	2
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	T-BiRD Therapy (All Patients) 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant).
Overall Study Adverse Event	8
Overall Study Death	1
Overall Study declined to participate	2
Overall Study still on therapy	1

Baseline Characteristics

Phase II Study of Thalidomide, Clarithromycin, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	T-BiRD Therapy (All Patients) n=26 Participants All patients that enrolled on the study and received treatment with T-BiRD are included in this analysis.
Age, Continuous	61 years n=93 Participants
Sex: Female, Male Female	11 Participants n=93 Participants
Sex: Female, Male Male	15 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	2 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	20 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants
Durie-Salmon Classification Stage 1A	12 participants n=93 Participants
Durie-Salmon Classification Stage 2A	9 participants n=93 Participants
Durie-Salmon Classification Stage 3A	5 participants n=93 Participants
Cytogenetics standard risk	18 participants n=93 Participants
Cytogenetics high risk	8 participants n=93 Participants
Immunoglobulins IgA myeloma	3 participants n=93 Participants
Immunoglobulins IgG myeloma	15 participants n=93 Participants
Immunoglobulins light chain only myeloma	8 participants n=93 Participants
karnofsky performance status 90% (or better)	12 participants n=93 Participants
karnofsky performance status 80%	12 participants n=93 Participants
karnofsky performance status 70%	2 participants n=93 Participants
International Staging System Classification Stage I	9 participants n=93 Participants
International Staging System Classification Stage II	13 participants n=93 Participants
International Staging System Classification Stage III	4 participants n=93 Participants
Hemoglobin at baseline (in g/dL)	11.95 g/dL n=93 Participants
serum creatinine at baseline (in mg/dL)	0.85 mg/dL n=93 Participants
platelet count at baseline (in 1000/uL)	241 1000/uL n=93 Participants
absolute neutrophil count at baseline (in 1000/uL)	3 1000/uL n=93 Participants
albumin at baseline (in mg/dL)	3.5 mg/dL n=93 Participants
lactage dehydrogenase at baseline (U/L)	151 U/L n=93 Participants
C-reactive protein at baseline (in mg/dL)	0.225 mg/dL n=93 Participants
Beta-2 microglobulin at baseline (in mg/L)	2.2 mg/L n=93 Participants

PRIMARY outcome

Timeframe: This was collected from patients for their duration on study treatment. Only the best response was recorded. Best responses were reported at any point of the study, from start of treatment up until removal of study, which occurred up to 57.4 cycles

Population: 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.

Outcome measures

Outcome measures
Measure	T-BiRD Therapy (All Patients) n=25 Participants 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant). 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.
Effect of Drug Combination on Multiple Myeloma sCR (stringent complete response)	2 participants
Effect of Drug Combination on Multiple Myeloma VGPR (very good partial response)	9 participants
Effect of Drug Combination on Multiple Myeloma PR (partial response)	9 participants
Effect of Drug Combination on Multiple Myeloma SD (stable disease)	5 participants

SECONDARY outcome

Timeframe: from baseline to cycle with maximum response

Population: 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.

Median Time to maximum response, reported in cycles of treatment. One cycle = 28 days.

Outcome measures

Outcome measures
Measure	T-BiRD Therapy (All Patients) n=25 Participants 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant). 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.
Median Time to Maximum Response	4 cycles Interval 1.0 to 7.0

SECONDARY outcome

Timeframe: from baseline to the time of first event that lead to removal from study (defined as progression, death, withdrawal of consent, or removal for toxicity)

Outcome measures

Outcome measures
Measure	T-BiRD Therapy (All Patients) n=26 Participants 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant). 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.
Event Free Survival	21.5 months Interval 4.2 to 57.4

SECONDARY outcome

Timeframe: From start of treatment, to the date of first progression

Population: 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.

Progression determined using International Myeloma Working Group criteria, as defined below. An increase of \> 25% from lowest response value one or more of the following: * Serum M-component and/or (the absolute increase must be \> 0.5 g/dL)\* * Urine M-component and/or (the absolute increase must be \> 200 mg/24 h) * Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be \> 10 mg/dL * Bone marrow plasma cell percentage; the absolute percentage must be \> 10% * Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas * Development of hypercalcaemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder \*if starting serum M protein is greater then 5 g/dL, absolute increase of 1g/dL is sufficient to determine relapse.

Outcome measures

Outcome measures
Measure	T-BiRD Therapy (All Patients) n=25 Participants 26 patients started the treatment phase. Per protocol, completion of the treatment phase was defined as removal from treatment due to progression, or to pursue an alternative treatment (either a stem cell transplant, or further consolidation chemotherapy in pursuit of a transplant). 25 of the 26 patients enrolled were accessible for response/progression, as one patient expired prior to first response assessment and could not be included in the analysis.
Progression Free Survival	35.6 months Interval 14.1 to n/a has been entered because this was not reached

Adverse Events

T-BiRD Therapy (All Patients)

Serious events: 9 serious events

Other events: 26 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	T-BiRD Therapy (All Patients) n=26 participants at risk All 26 patients that were enrolled onto the study were assessed for adverse events.
Musculoskeletal and connective tissue disorders muscle weakness	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
General disorders dizziness/fall	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Blood and lymphatic system disorders atrial fibrillation	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Skin and subcutaneous tissue disorders rash (steven johnson syndrome)	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Musculoskeletal and connective tissue disorders multiple compression fractures	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Renal and urinary disorders renal insufficiency/Congestive heart failure	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Musculoskeletal and connective tissue disorders chest pain	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Vascular disorders deep vein thrombosis	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Cardiac disorders myocardial infarction	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Infections and infestations upper respiratory infection	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Infections and infestations sepsis	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Infections and infestations fever	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).

Other adverse events

Other adverse events
Measure	T-BiRD Therapy (All Patients) n=26 participants at risk All 26 patients that were enrolled onto the study were assessed for adverse events.
Blood and lymphatic system disorders lymphopenia	100.0% 26/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Blood and lymphatic system disorders neutropenia	30.8% 8/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Blood and lymphatic system disorders anemia	23.1% 6/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Blood and lymphatic system disorders thrombocytopenia	11.5% 3/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Blood and lymphatic system disorders leukopenia	7.7% 2/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Skin and subcutaneous tissue disorders skin rash	53.8% 14/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Infections and infestations unspecified infection	42.3% 11/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Metabolism and nutrition disorders anorexia/dysgeusia	38.5% 10/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
General disorders dizziness	26.9% 7/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Metabolism and nutrition disorders hyperglycemia	19.2% 5/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Psychiatric disorders psychomotor agitation	7.7% 2/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Vascular disorders deep vein thrombosis	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
Infections and infestations bacterial pneumonia	3.8% 1/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).
General disorders weakness	38.5% 10/26 • Adverse events (serious and non-serious) were recorded from first dose of study drug, until removal from study (treatment).

Additional Information

Jennifer Hess

Weill Cornell Medical College

Phone: 6469629440

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60