Lenalidomide and Dexamethasone With or Without Anakinra in Treating Patients With Early Stage Multiple Myeloma

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02492750
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 41.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This partially randomized phase I/II trial studies the side effects and best dose of anakinra when given together with lenalidomide and dexamethasone in treating patients with early stage multiple myeloma. Biological therapies, such as lenalidomide and anakinra, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether lenalidomide and dexamethasone are more effective with or without anakinra in treating patients with multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Indolent Plasma Cell Myeloma; Plasma Cell Myeloma; Smoldering Plasma Cell Myeloma	Biological: Anakinra; Drug: Dexamethasone; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Placebo	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the maximum tolerated dose (MTD)/maximum allowable dose (MAD) of anakinra that can be combined with lenalidomide and dexamethasone. (Phase I) II. To compare the time to progression of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra). (Phase II)

SECONDARY OBJECTIVES:

1. To compare the response rate of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

2. To compare the toxicity of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

3. To compare the overall survival of the standard treatment arm (lenalidomide/dexamethasone) to the experimental arm (lenalidomide/dexamethasone + anakinra).

OUTLINE: This is a phase I, dose-escalation study of anakinra followed by a phase II study.

PHASE I: Patients receive lenalidomide orally (PO) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra subcutaneously (SC) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phase I/II Double Blind Randomized Trial of Lenalidomide/Dexamethasone/Anakinra vs. Lenalidomide/Dexamethasone/Placebo in Patients With Early Stage Multiple Myeloma and High Plasma Cell Growth Rate
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Jun 5, 2019
• Actual Study Completion Date: Sep 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (lenalidomide, dexamethasone, anakinra) Patients receive lenalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22. Patients also receive anakinra SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity	Biological: Anakinra; Given SC; Other Names: Kinaret Kineret rIL-1ra rIL1RN ; Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid
Active Comparator: Arm B (lenalidomide, dexamethasone, placebo) Patients receive lenalidomide and dexamethasone as in Arm A. Patients also receive placebo SC on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Dexamethasone; Given PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Lenalidomide; Given PO; Other Names: CC-5013 CC5013 CDC 501 Revlimid ; Other: Placebo; Given SC; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. Number of Participants Experiencing a Dose-limiting Toxicity (DLT) [28 days]

   Number of participants experiencing a dose-limiting toxicity (DLT) is reported below. Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

2. Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0 [Up to 41 months]

   The number of participants who experienced at least one grade 3+ adverse events deemed at least possibly related to treatment, graded according to NCI CTCAE version 4.0, is reported below.

3. Best Response [Up to 41 months]

   The following response terms will be used: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD). The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. PR defined as: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24hrs; ≥ 50% reduction in the size of soft tissue plasmacytomas. MR defined as: ≥25% but ≤ 49% reduction of serum M protein and reduction in 24-hour urine M-protein by 50-89% which still exceeds 200mg/24 hours; 25-49% reduction in the size of soft tissue plasmacytoma and No increase in the size or number of lytic bone lesions. VGPR defined as: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Absolute neutrophil count (ANC) >= 1700/mm^3

• Platelet count >= 100,000/mm^3

• Hemoglobin >= 8.0 g/dL

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 3 x upper limit of normal (ULN)

• Creatinine clearance >= 30 mL/min (as determined by Cockroft-Gault equation)

• Diagnosis of multiple myeloma according to International Myeloma Working Group criteria and one of the following:

• Smoldering multiple myeloma (SMM)

• Indolent multiple myeloma (IMM)

• Newly diagnosed multiple myeloma (MM)

• Note: patients with lytic disease and anemia are eligible

• High risk disease defined by all of the following:

• = 10% bone marrow plasma cells AND

• Abnormal serum free light chain (FLC) ratio (< 0.26 or > 1.65) by serum FLC assay AND

• Monotypic plasma cell S-phase >= 0.3%

• Measurable level of M-protein > 1 g/dL on serum protein electrophoresis or > 200 mg of M-protein on a 24 hour urine protein electrophoresis

• Negative tuberculosis (TB) testing (Quantiferon - TB blood test or skin test) =< 7 days prior to registration

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

• Provide signed informed consent

• Negative (serum or urine) pregnancy test done =< 7 days prior to registration, for women of childbearing potential only; NOTE: a second pregnancy test must be performed within 24 hours prior to the start of lenalidomide; the subject may not receive lenalidomide until the study doctor has verified that the results of these pregnancy tests are negative

• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

• Willing and able to comply with the requirements of the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program

• Females of childbearing potential must be willing to adhere to the scheduled pregnancy testing as required by the Revlimid REMS program

Exclusion Criteria:

• Prior treatment with any other agent that may affect M-protein =< 30 days prior to registration

• Acute/chronic infections, open wounds, or any active infection requiring intravenous antibiotic therapy =< 12 weeks prior to registration

• Other active malignancy (=< 3 years) prior to registration; exceptions: basal cell skin cancer or carcinoma-in-situ of the cervix or low-risk prostate cancer after curative therapy

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequate contraception

• New York Heart Association (NYHA) class 3 or 4 congestive heart failure (CHF) symptoms

• Other concurrent chemotherapy, radiotherapy, or any ancillary therapy considered investigational; NOTE: bisphosphonates are allowed while on protocol treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Lust, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 19, 2018

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02492750
• Other Study ID Numbers: MC138B; NCI-2015-01041; RV-CL-MM-PI-004334; MC138B; P30CA015083
• First Posted: Jul 9, 2015
• Last Update Posted: Mar 25, 2020
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma; Dexamethasone; Dexamethasone acetate; Lenalidomide; Interleukin 1 Receptor Antagonist Protein; Ichthammol; BB 1101

Study Results

Participant Flow

Arm/Group Title	Phase I - Dose Level 1	Phase I - Dose Level 2	Phase I - Dose Level 3
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.
Period Title: Overall Study
STARTED	4	4	6
COMPLETED	4	4	6
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phase I - Dose Level 1	Phase I - Dose Level 2	Phase I - Dose Level 3	Total
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Total of all reporting groups
Overall Participants	4	4	6	14
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67	62.5	58.5	60
Sex: Female, Male (Count of Participants)
Female	2 50%	1 25%	1 16.7%	4 28.6%
Male	2 50%	3 75%	5 83.3%	10 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	4 100%	6 100%	14 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
ISS Stage of myeloma at diagnosis (Count of Participants)
I	1 25%	0 0%	5 83.3%	6 42.9%
II	1 25%	1 25%	1 16.7%	3 21.4%
ECOG Performance Score at baseline (Count of Participants)
0	3 75%	2 50%	6 100%	11 78.6%
1	1 25%	2 50%	0 0%	3 21.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
Description	Number of participants experiencing a dose-limiting toxicity (DLT) is reported below. Dose-limiting toxicity is graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I - Dose Level 1	Phase I - Dose Level 2	Phase I - Dose Level 3
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.
Measure Participants	4	4	6
Count of Participants [Participants]	0 0%	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase I - Dose Level 1, Phase I - Dose Level 2, Phase I - Dose Level 3
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose (MTD) Level
	Estimated Value	3
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MTD is defined as the dose level below the lowest dose that induces DLT in at least one-third of patients. A total of 6 patients treated at the MTD will be sufficient to identify common toxicities at the MTD.

2. Primary Outcome

Title	Number of Participants Who Experienced at Least One Grade 3+ Adverse Events Deemed at Least Possibly Related to Treatment, Graded According to NCI CTCAE Version 4.0
Description	The number of participants who experienced at least one grade 3+ adverse events deemed at least possibly related to treatment, graded according to NCI CTCAE version 4.0, is reported below.
Time Frame	Up to 41 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I - Dose Level 1	Phase I - Dose Level 2	Phase I - Dose Level 3
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.
Measure Participants	4	4	6
Count of Participants [Participants]	2 50%	3 75%	3 50%

3. Primary Outcome

Title	Best Response
Description	The following response terms will be used: stringent Complete Response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), Minimal Response (MR), stable disease (SD), and progressive disease (PD). The International Myeloma Working Group (IMWG) uniform response criteria (Rajkumar et al, 2011) will be used to assess response to therapy. PR defined as: ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24hrs; ≥ 50% reduction in the size of soft tissue plasmacytomas. MR defined as: ≥25% but ≤ 49% reduction of serum M protein and reduction in 24-hour urine M-protein by 50-89% which still exceeds 200mg/24 hours; 25-49% reduction in the size of soft tissue plasmacytoma and No increase in the size or number of lytic bone lesions. VGPR defined as: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein <100 mg/24 h
Time Frame	Up to 41 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I - Dose Level 1	Phase I - Dose Level 2	Phase I - Dose Level 3
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.
Measure Participants	4	4	6
Partial Response (PR)	2 50%	3 75%	3 50%
Minimal Response (MR)	1 25%	1 25%	2 33.3%
Very Good Partial Response (VGPR)	1 25%	0 0%	1 16.7%

Adverse Events

Time Frame	Up to 41 months
Arm/Group Title	Phase I - Dose Level 1		Phase I - Dose Level 2		Phase I - Dose Level 3
Arm/Group Description	Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive the starting dose of 100 mg anakinra SQ every third day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.		Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every other day. Participants also receive 325 mg aspirin PO per day with food on days 1-28.		Participants receive 25 mg lenalidomide PO on days 1-21; SMM and IMM participants receive 20 mg dexamethasone PO on days 1, 8, 15, and 22; Active MM participants receive 40 mg dexamethasone PO on days 1, 8, 15, and 22. Participants also receive 100 mg anakinra SQ every day on days 1-28. Participants also receive 325 mg aspirin PO per day with food on days 1-28.
All Cause Mortality
	Phase I - Dose Level 1		Phase I - Dose Level 2		Phase I - Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		1/6 (16.7%)
Serious Adverse Events
	Phase I - Dose Level 1		Phase I - Dose Level 2		Phase I - Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/4 (25%)		1/6 (16.7%)
Infections and infestations
Lung infection	1/4 (25%)	1	0/4 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Vascular disorders
Thromboembolic event	1/4 (25%)	1	0/4 (0%)	0	1/6 (16.7%)	1
Other (Not Including Serious) Adverse Events
	Phase I - Dose Level 1		Phase I - Dose Level 2		Phase I - Dose Level 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		4/4 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anemia	4/4 (100%)	60	3/4 (75%)	8	3/6 (50%)	19
Gastrointestinal disorders
Constipation	2/4 (50%)	23	4/4 (100%)	24	5/6 (83.3%)	11
Diarrhea	2/4 (50%)	35	3/4 (75%)	12	5/6 (83.3%)	20
Dry mouth	1/4 (25%)	2	0/4 (0%)	0	0/6 (0%)	0
Nausea	2/4 (50%)	26	1/4 (25%)	1	2/6 (33.3%)	2
Vomiting	0/4 (0%)	0	1/4 (25%)	1	1/6 (16.7%)	1
General disorders
Fatigue	4/4 (100%)	71	3/4 (75%)	13	3/6 (50%)	18
Injection site reaction	4/4 (100%)	8	4/4 (100%)	12	5/6 (83.3%)	15
Infections and infestations
Mucosal infection	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Investigations
Creatinine increased	1/4 (25%)	1	0/4 (0%)	0	2/6 (33.3%)	2
Lymphocyte count decreased	3/4 (75%)	10	3/4 (75%)	13	2/6 (33.3%)	9
Neutrophil count decreased	3/4 (75%)	32	3/4 (75%)	27	5/6 (83.3%)	24
Platelet count decreased	3/4 (75%)	41	2/4 (50%)	7	0/6 (0%)	0
White blood cell decreased	3/4 (75%)	13	2/4 (50%)	11	2/6 (33.3%)	16
Metabolism and nutrition disorders
Hyperglycemia	1/4 (25%)	3	0/4 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/4 (25%)	1	0/4 (0%)	0	0/6 (0%)	0
Nervous system disorders
Dysgeusia	0/4 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	3
Peripheral sensory neuropathy	1/4 (25%)	5	2/4 (50%)	29	4/6 (66.7%)	20
Psychiatric disorders
Agitation	1/4 (25%)	1	0/4 (0%)	0	1/6 (16.7%)	1
Delusions	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Euphoria	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Insomnia	4/4 (100%)	55	4/4 (100%)	39	5/6 (83.3%)	28
Renal and urinary disorders
Chronic kidney disease	2/4 (50%)	4	0/4 (0%)	0	1/6 (16.7%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	3/4 (75%)	6	3/4 (75%)	7	0/6 (0%)	0
Urticaria	0/4 (0%)	0	1/4 (25%)	1	0/6 (0%)	0
Vascular disorders
Thromboembolic event	1/4 (25%)	7	0/4 (0%)	0	0/6 (0%)	0

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.