A Study for Patients That Have Been Previously Been Treated in Waldenstrom's Macroglobulinemia or Multiple Myeloma

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00718419
• Collaborator: (none)
• Enrollment: 56
• Locations: 4
• Arm: 1
• Duration (Months): 49
• Patients Per Site: 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

To determine whether further study of single-agent enzastaurin is warranted in patients with previously treated Waldenstrom's Macroglobulinemia or Multiple Myeloma based on response.

Condition or Disease	Intervention/Treatment	Phase
Waldenstrom's Macroglobulinemia; Multiple Myeloma	Drug: Enzastaurin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter Phase 2 Study of Single-Agent Enzastaurin HCl in Previously Treated Waldenstrom's Macroglobulinemia or Multiple Myeloma
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A: Enzastaurin	Drug: Enzastaurin; Enzastaurin: Cycle 1 Day 1 only: 3, 125-milligrams (mg) tablets three times on Day 1 (Day 1 total dose = 1125 mg) Day 2 onwards and subsequent Cycles: 2, 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days. Patients may stay on drug past 8 cycles, (until the study is closed) or until disease progression.; Other Names: LY317615

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate) [Baseline to measured progressive disease up to 40.51 months]

   European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria (RC) used for MM. CR: no serum/urine M protein for 6 weeks (wk), <5% plasma cells in bone marrow (PCBM), no lytic bone lesions (LBL) size/number increase, no soft tissue plasmacytomas (STPC); PR: met some CR criteria plus maintain for 6 wk ≥50% serum monoclonal paraprotein (SPEP) and PCBM decrease, either decrease of ≥90% or <200 mg light chain excretion (LCE), ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk, a decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. International Workshop on WM (IWWM) RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% immunoglobulin M (IgM) and adenopathy/organomegaly (A/O) decrease; no new symptoms of WM. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical symptoms of WM.

Secondary Outcome Measures

1. Duration of Response (DOR) [Time of response to time of measured progressive disease up to 38.37 months]

   DOR is defined as elapsed time from the first evidence of CR, PR, MR or MinR until date of progression of disease (PD). EBMT RC used for MM. CR: no serum/urine M protein for 6 wk, <5% PCBM, no LBL size/number increase, no STPC; PR: met some CR criteria plus maintain for 6 wk ≥50% SPEP and PCBM decrease, either decrease of ≥90% or <200 mg LCE, ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. PD: >25% increase in SPEP, 24 hour urinary LCE, PCBM, STPC size increase, new bone lesion or STPC. IWWM RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% IgM and A/O decrease; no new WM symptoms. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical of WM symptoms. PD: >25% IgM increase, progression of clinical findings or symptoms. For participants who had no PD, DOR was censored at their last contact.

2. Time to Progressive Disease [Baseline to measured progressive disease up to 40.51 months]

   Time to progression is defined as the elapsed time from the date of study enrollment to the date of objectively determined progressive disease (PD). European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria was used for MM. PD: >25% increase in serum monoclonal paraprotein (SPEP), 24 hour urinary light chain excretion (LCE), plasma cells in bone marrow (PCBM), soft tissue plasmacytomas (STPC) size increase, new bone lesion or STPC. International Workshop on WM (IWWM) Response Criteria was used for WM. PD: >25% immunoglobulin M (IgM) increase, progression of clinical findings or symptoms. For participants who had no PD, time to PD was censored at their last contact.

3. Number of Participants With Adverse Events (Safety and Adverse Events) [Treatment start to 30 days after discontinuation of study treatment up to 23.40 months]

   Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 23.40 months.

Other Outcome Measures

1. Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment [Study treatment discontinuation up to 30 days post study treatment discontinuation]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• At least 18 years of age.

• Patients must have Waldenstrom's Macroglobulinemia (WM) or Multiple Myeloma (MM) previously treated with at least 1 and no more than 5 prior therapies.

• Treatment with prior autologous transplant is permitted. If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy.

• Patients with MM must have a monoclonal protein in the serum of greater than or equal to 1 gram per deciliter (g/dL) or monoclonal light chain in the urine protein electrophoresis of greater than or equal to 200 milligrams (mg)/ 24 hours, or measurable plasmacytoma.

• Patients with WM must have an immunoglobulin M (IgM) paraprotein with a minimum IgM level of > 2 times the upper limit of normal (ULN), have detectable lymphoplasmacytic (LPL) cells in the bone marrow, and be symptomatic for WM.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2.

• The following laboratory values obtained prior to registration:

• Absolute neutrophil count (ANC) greater than or equal to 1000/microliter

• Platelet (PLT) count greater than or equal to 75,000/microliter

• Total bilirubin less than or equal to 1.5 x ULN (if total is elevated check direct and, if normal, patient is eligible)

• Aspartate transaminase (AST) less than or equal to 3 x ULN

• Creatinine less than or equal to 1.5 x ULN

• Hemoglobin (Hgb) greater than or equal to 8.0 g/dL.

• Expected survival of greater than 12 weeks.

• The ability to provide informed consent.

• Male and female patients with reproductive potential must use an approved contraceptive method, if appropriate (for example, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after discontinuation of study treatment. Women with childbearing potential must have a negative serum pregnancy test less than or equal to 3 days prior to study enrollment

Exclusion Criteria:

• Prior allogeneic hematopoietic stem cell transplant.

• Are unable to discontinue use of non-Enzyme-Inducing Anti-Epileptic Drugs (EIAEDs), for example carbamazepine, phenobarbital, and phenytoin. Patients on anti-coagulant therapy should be monitored. Ongoing treatment with therapeutic doses of Coumadin is prohibited. However, prophylactic, low dose (less than or equal to 2 mg daily) Coumadin for deep venous thrombosis (DVT) is allowed. In such cases, prothrombin time/ international normalized ratio (PT/INR) should be closely monitored.

• Have electrocardiogram (ECG) abnormalities including baseline 12-lead ECG with QTc interval of greater than 450 milliseconds (msec) in males or greater than 470 msec in females, or QRS duration of greater than 100 msec. Patients who have a congenital long-QT-syndrome in their own or family medical history should be excluded at the investigator's discretion.

• Have an uncontrolled infection.

• Have prior treatment with Carmustine (BCNU) 6 weeks, alkylating agent 4 weeks, or other cytotoxic chemotherapy agents 4 weeks prior to registration in this trial. Have prior treatment with biologic therapy less than or equal to 12 weeks or corticosteroids less than or equal to 2 weeks prior to registration in this trial. However, treatment with less than or equal to 10 mg of prednisone as a chronic therapy is allowed.

• Have radiation therapy less than or equal to 2 weeks prior to treatment in this trial.

• Are pregnant or breast-feeding.

• Are being treated with concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational.

• Are known to be human immunodeficiency virus (HIV) positive.

• Were previously treated with enzastaurin.

• Patients who are unable to swallow tablets.

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.

• Concurrent malignancy that could complicate interpretation of response or safety evaluation. Non-melanoma skin cancer and carcinoma in situ of the cervix are not exclusions.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Boston	Massachusetts	United States	02115
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	La Roche Sur Yon		France	85925
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nantes		France	44093
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nimes		France	30029

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon- Fri 9 AM- 5 PM Eastern time (UTC/GMT- 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Lilly Clinical Trial Registry

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT00718419
• Other Study ID Numbers: 11481; H6Q-MC-S042
• First Posted: Jul 18, 2008
• Last Update Posted: Sep 3, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Eli Lilly and Company: Waldenstrom's Macroglobulinemia; Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Waldenstrom Macroglobulinemia

Study Results

Participant Flow

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Period Title: Overall Study
STARTED	14	42
Received at Least One Dose of Study Drug	14	42
COMPLETED	1	3
NOT COMPLETED	13	39

Baseline Characteristics

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)	Total
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Total of all reporting groups
Overall Participants	14	42	56
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.28 (7.51)	64.57 (8.53)	66.7 (9.06)
Sex: Female, Male (Count of Participants)
Female	6 42.9%	7 16.7%	13 23.2%
Male	8 57.1%	35 83.3%	43 76.8%
Race/Ethnicity, Customized (Count of Participants)
African	0 0%	1 2.4%	1 1.8%
Caucasian	14 100%	41 97.6%	55 98.2%
Region of Enrollment (Count of Participants)
France	14 100%	5 11.9%	19 33.9%
United States	0 0%	37 88.1%	37 66.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Complete Response (CR), Partial Response (PR) and Minimal Response (MR) or Minor Response (MinR): (Response Rate)
Description	European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria (RC) used for MM. CR: no serum/urine M protein for 6 weeks (wk), <5% plasma cells in bone marrow (PCBM), no lytic bone lesions (LBL) size/number increase, no soft tissue plasmacytomas (STPC); PR: met some CR criteria plus maintain for 6 wk ≥50% serum monoclonal paraprotein (SPEP) and PCBM decrease, either decrease of ≥90% or <200 mg light chain excretion (LCE), ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk, a decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. International Workshop on WM (IWWM) RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% immunoglobulin M (IgM) and adenopathy/organomegaly (A/O) decrease; no new symptoms of WM. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical symptoms of WM.
Time Frame	Baseline to measured progressive disease up to 40.51 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug.

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Measure Participants	14	42
Number [percentage of participants]	7.1 50.7%	38.1 90.7%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as elapsed time from the first evidence of CR, PR, MR or MinR until date of progression of disease (PD). EBMT RC used for MM. CR: no serum/urine M protein for 6 wk, <5% PCBM, no LBL size/number increase, no STPC; PR: met some CR criteria plus maintain for 6 wk ≥50% SPEP and PCBM decrease, either decrease of ≥90% or <200 mg LCE, ≥50% STPC size decrease; MR: met some PR criteria plus maintain for 6 wk decrease of: 25-49% SPEP, 50-89% 24 hour urinary LCE, 25-49% PCBM, 25-49% STPC size. PD: >25% increase in SPEP, 24 hour urinary LCE, PCBM, STPC size increase, new bone lesion or STPC. IWWM RC used for WM. CR: no serum M protein, malignant cells in BM, or lymphadenopathy/organomegaly; PR: ≥50% IgM and A/O decrease; no new WM symptoms. MinR: ≥25% to <50% IgM decrease, no A/O progression; no cytopenias or clinical of WM symptoms. PD: >25% IgM increase, progression of clinical findings or symptoms. For participants who had no PD, DOR was censored at their last contact.
Time Frame	Time of response to time of measured progressive disease up to 38.37 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug and had complete response (CR) or partial response (PR) or minimal response (MR) or minor response (MinR). The numbers of participants censored are 1 (MM) and 13 (WM).

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Measure Participants	1	16
Median (95% Confidence Interval) [months]	NA	NA

3. Secondary Outcome

Title	Time to Progressive Disease
Description	Time to progression is defined as the elapsed time from the date of study enrollment to the date of objectively determined progressive disease (PD). European Group for Blood and Bone Marrow Transplant (EBMT) Response Criteria was used for MM. PD: >25% increase in serum monoclonal paraprotein (SPEP), 24 hour urinary light chain excretion (LCE), plasma cells in bone marrow (PCBM), soft tissue plasmacytomas (STPC) size increase, new bone lesion or STPC. International Workshop on WM (IWWM) Response Criteria was used for WM. PD: >25% immunoglobulin M (IgM) increase, progression of clinical findings or symptoms. For participants who had no PD, time to PD was censored at their last contact.
Time Frame	Baseline to measured progressive disease up to 40.51 months

Outcome Measure Data

Analysis Population Description

All participants who had at least one dose of the study drug. The numbers of participants censored are 7 (MM) and 33 (WM).

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Measure Participants	14	42
Median (95% Confidence Interval) [months]	5.11	27.73

4. Secondary Outcome

Title	Number of Participants With Adverse Events (Safety and Adverse Events)
Description	Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 23.40 months.
Time Frame	Treatment start to 30 days after discontinuation of study treatment up to 23.40 months

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug.

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Measure Participants	14	42
Serious Adverse Events	4 28.6%	9 21.4%
Other Nonserious Adverse Events	12 85.7%	42 100%

5. Other Pre-specified Outcome

Title	Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment
Time Frame	Study treatment discontinuation up to 30 days post study treatment discontinuation

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of the study drug.

Arm/Group Title	Multiple Myeloma (MM)	Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.	Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
Measure Participants	14	42
Count of Participants [Participants]	0 0%	1 2.4%

Adverse Events

Adverse Event Reporting Description	Deaths due to progressive disease are not considered adverse events; however they are reported in the Participant Flow for those who died during the study and in the Other Pre-Specified Outcome Measure for those who died during the 30-day post study treatment follow-up period.
Arm/Group Title	Multiple Myeloma (MM)		Waldenstrom's Macroglobulinemia (WM)
Arm/Group Description	Participants diagnosed with MM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.		Participants diagnosed with WM received: Three 125-milligrams (mg) Enzastaurin tablets three times on Day 1 of Cycle 1 (Day 1 total dose = 1125 mg). Day 2 onwards and subsequent Cycles: Two 125-mg tablets orally twice a day (500 mg total per day). Cycle length (all cycles): 28 days.
All Cause Mortality
	Multiple Myeloma (MM)		Waldenstrom's Macroglobulinemia (WM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Multiple Myeloma (MM)		Waldenstrom's Macroglobulinemia (WM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/14 (28.6%)		9/42 (21.4%)
Blood and lymphatic system disorders
Anaemia	1/14 (7.1%)	1	0/42 (0%)	0
Haemolytic anaemia	0/14 (0%)	0	1/42 (2.4%)	1
Thrombocytopenia	0/14 (0%)	0	1/42 (2.4%)	1
Cardiac disorders
Cardiac failure	1/14 (7.1%)	1	0/42 (0%)	0
Myocardial infarction	1/14 (7.1%)	1	0/42 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/14 (0%)	0	1/42 (2.4%)	1
Intestinal obstruction	0/14 (0%)	0	1/42 (2.4%)	1
Nausea	0/14 (0%)	0	1/42 (2.4%)	1
Peritoneal haemorrhage	0/14 (0%)	0	1/42 (2.4%)	1
Volvulus	0/14 (0%)	0	1/42 (2.4%)	1
Vomiting	0/14 (0%)	0	1/42 (2.4%)	1
General disorders
Asthenia	0/14 (0%)	0	1/42 (2.4%)	1
Chest pain	1/14 (7.1%)	1	0/42 (0%)	0
General physical health deterioration	1/14 (7.1%)	1	0/42 (0%)	0
Infections and infestations
Abscess	0/14 (0%)	0	1/42 (2.4%)	1
Clostridium difficile colitis	0/14 (0%)	0	1/42 (2.4%)	2
Pneumocystis jiroveci pneumonia	1/14 (7.1%)	2	1/42 (2.4%)	1
Sepsis	0/14 (0%)	0	1/42 (2.4%)	1
Septic shock	0/14 (0%)	0	1/42 (2.4%)	1
Injury, poisoning and procedural complications
Wound	0/14 (0%)	0	1/42 (2.4%)	1
Metabolism and nutrition disorders
Dehydration	0/14 (0%)	0	1/42 (2.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/14 (0%)	0	1/42 (2.4%)	1
Muscular weakness	0/14 (0%)	0	1/42 (2.4%)	1
Nervous system disorders
Iiird nerve paralysis	0/14 (0%)	0	1/42 (2.4%)	1
Syncope	0/14 (0%)	0	1/42 (2.4%)	1
Renal and urinary disorders
Renal failure acute	1/14 (7.1%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/14 (7.1%)	1	0/42 (0%)	0
Bronchopneumopathy	1/14 (7.1%)	1	0/42 (0%)	0
Dyspnoea	0/14 (0%)	0	1/42 (2.4%)	1
Vascular disorders
Thrombophlebitis	0/14 (0%)	0	1/42 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Multiple Myeloma (MM)		Waldenstrom's Macroglobulinemia (WM)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/14 (85.7%)		42/42 (100%)
Blood and lymphatic system disorders
Anaemia	6/14 (42.9%)	6	14/42 (33.3%)	15
Leukopenia	0/14 (0%)	0	8/42 (19%)	8
Neutropenia	1/14 (7.1%)	1	6/42 (14.3%)	6
Thrombocytopenia	2/14 (14.3%)	2	6/42 (14.3%)	7
Ear and labyrinth disorders
Vertigo	2/14 (14.3%)	6	0/42 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/14 (7.1%)	1	0/42 (0%)	0
Constipation	0/14 (0%)	0	3/42 (7.1%)	3
Diarrhoea	4/14 (28.6%)	9	3/42 (7.1%)	3
Nausea	5/14 (35.7%)	11	2/42 (4.8%)	2
Vomiting	1/14 (7.1%)	2	2/42 (4.8%)	2
General disorders
Asthenia	3/14 (21.4%)	7	3/42 (7.1%)	3
Chest pain	1/14 (7.1%)	1	0/42 (0%)	0
Fatigue	5/14 (35.7%)	7	22/42 (52.4%)	23
Malaise	1/14 (7.1%)	1	0/42 (0%)	0
Oedema	1/14 (7.1%)	1	1/42 (2.4%)	1
Pain	2/14 (14.3%)	4	1/42 (2.4%)	1
Pyrexia	4/14 (28.6%)	8	3/42 (7.1%)	3
Infections and infestations
Bronchitis	2/14 (14.3%)	4	0/42 (0%)	0
Cystitis	1/14 (7.1%)	1	0/42 (0%)	0
Fungal infection	1/14 (7.1%)	1	0/42 (0%)	0
Herpes zoster	1/14 (7.1%)	1	0/42 (0%)	0
Nasopharyngitis	2/14 (14.3%)	2	0/42 (0%)	0
Pharyngitis	1/14 (7.1%)	1	0/42 (0%)	0
Sinusitis	0/14 (0%)	0	4/42 (9.5%)	5
Tooth abscess	1/14 (7.1%)	1	0/42 (0%)	0
Upper respiratory tract infection	0/14 (0%)	0	4/42 (9.5%)	4
Urinary tract infection	2/14 (14.3%)	2	0/42 (0%)	0
Injury, poisoning and procedural complications
Head injury	1/14 (7.1%)	1	0/42 (0%)	0
Investigations
Aspartate aminotransferase increased	0/14 (0%)	0	3/42 (7.1%)	3
Electrocardiogram qt prolonged	1/14 (7.1%)	1	0/42 (0%)	0
Weight decreased	2/14 (14.3%)	2	1/42 (2.4%)	1
Metabolism and nutrition disorders
Decreased appetite	1/14 (7.1%)	1	1/42 (2.4%)	1
Hypercalcaemia	1/14 (7.1%)	1	1/42 (2.4%)	1
Hyperglycaemia	1/14 (7.1%)	1	9/42 (21.4%)	10
Hypoglycaemia	0/14 (0%)	0	3/42 (7.1%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	0/14 (0%)	0	4/42 (9.5%)	4
Back pain	1/14 (7.1%)	1	0/42 (0%)	0
Bone pain	1/14 (7.1%)	1	0/42 (0%)	0
Musculoskeletal pain	1/14 (7.1%)	1	1/42 (2.4%)	1
Myalgia	3/14 (21.4%)	3	0/42 (0%)	0
Neck pain	1/14 (7.1%)	1	0/42 (0%)	0
Osteoporosis	1/14 (7.1%)	1	0/42 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma	1/14 (7.1%)	1	0/42 (0%)	0
Nervous system disorders
Aphonia	1/14 (7.1%)	1	0/42 (0%)	0
Dizziness	1/14 (7.1%)	1	9/42 (21.4%)	9
Head discomfort	1/14 (7.1%)	2	0/42 (0%)	0
Headache	1/14 (7.1%)	1	5/42 (11.9%)	6
Hypoaesthesia	1/14 (7.1%)	1	0/42 (0%)	0
Neuralgia	1/14 (7.1%)	1	0/42 (0%)	0
Parkinson's disease	1/14 (7.1%)	1	0/42 (0%)	0
Peripheral sensory neuropathy	1/14 (7.1%)	1	0/42 (0%)	0
Tremor	1/14 (7.1%)	2	2/42 (4.8%)	2
Psychiatric disorders
Apathy	1/14 (7.1%)	1	0/42 (0%)	0
Depression	1/14 (7.1%)	1	2/42 (4.8%)	2
Insomnia	4/14 (28.6%)	11	1/42 (2.4%)	1
Renal and urinary disorders
Nephropathy toxic	1/14 (7.1%)	1	0/42 (0%)	0
Renal failure	1/14 (7.1%)	1	0/42 (0%)	0
Renal pain	1/14 (7.1%)	1	0/42 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/14 (21.4%)	3	3/42 (7.1%)	3
Dyspnoea	0/14 (0%)	0	3/42 (7.1%)	3
Dyspnoea exertional	1/14 (7.1%)	1	1/42 (2.4%)	1
Epistaxis	1/14 (7.1%)	4	4/42 (9.5%)	4
Pneumonitis	1/14 (7.1%)	1	0/42 (0%)	0
Skin and subcutaneous tissue disorders
Ingrowing nail	1/14 (7.1%)	1	0/42 (0%)	0
Night sweats	0/14 (0%)	0	3/42 (7.1%)	3
Rash	2/14 (14.3%)	2	1/42 (2.4%)	1
Swelling face	1/14 (7.1%)	1	0/42 (0%)	0
Vascular disorders
Phlebitis	1/14 (7.1%)	1	0/42 (0%)	0
Thrombosis	1/14 (7.1%)	1	0/42 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.