Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00935792
• Collaborator: (none)
• Enrollment: 28
• Locations: 2
• Arm: 1
• Duration (Months): 77
• Patients Per Site: 14
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the signaling molecules needed for cell growth. Monoclonal antibodies, such as alemtuzumab, can bind to and kill malignant lymphocytes.

PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with alemtuzumab and will see how well they work in treating patients with recurrent chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL).

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Leukemia	Drug: alemtuzumab; Drug: everolimus	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES: I. Test the safety and tolerability of the combination of everolimus and alemtuzumab. (Phase I) II. Determine the maximum tolerated dose of everolimus in this combination. (Phase I) III. Assess the rate of overall responses in patients with relapsed/refractory CLL to treatment with the maximum tolerated dose of everolimus together with a standard dose of alemtuzumab using conventional NCI-WG 1996 response criteria. (Phase

1. 1. To assess the complete responses to this combination regimen using conventional NCI-WG 1996 criteria and an expanded definition of response, including CT scans of chest-abdomen-pelvis, immunohistochemical analysis for residual disease in the bone marrow, and sensitive flow cytometry for minimal residual disease in patients in complete clinical remission. V. To monitor and assess toxicity of this regimen. SECONDARY OBJECTIVES: I. To determine the overall and progression-free survival, duration of response, and time to next treatment. II. To assess the correlation between the individual prognostic markers (17p-, p53 gene mutations, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+, CD49d, B2 microglobulin) and clinical outcome. III. Serial measurement of clinical status and lymphocyte counts to test the rate of reduction in CLL tumor burden. TERTIARY OBJECTIVES: I. Determine the effect of everolimus on the sensitivity of CLL cells to alemtuzumab CDC and ADCC. II. Determine the effect of everolimus on the CLL cell-stroma interaction. III. Detail the in vivo effect of the everolimus-alemtuzumab regimen on critical aspects of the immune system in CLL. OUTLINE: This is a phase I, dose escalation study of everolimus followed by a phase II study. Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 7 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Everolimus (RAD001) and Alemtuzumab: A Phase I/II Study
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Dec 1, 2015
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Drug: alemtuzumab; Given subcutaneously; Other Names: anti-CD52 monoclonal antibody MoAb CD52 Monoclonal Antibody Campath-1H Campath-1H Monoclonal Antibody CD52 Campath ; Drug: everolimus; Given orally; Other Names: Certican RAD001 42-O-(2-Hydroxy)ethyl Rapamycin

Outcome Measures

Primary Outcome Measures

1. Clinical Response (Complete or Partial Remission) [After 2 courses of treatment]

   CR requires all of the following for a period of at least 2months:Absence of lymphadenopathy.No hepatomegaly or splenomegaly.Absence of constitutional symptoms.• Neutrophils>1500/ul•Platelets>100,000/ul • Hemoglobin >11.0gm/dl• Peripheral blood lymphocytes <4000/uLBonemarrow. normocellular with<30%of nucleated cells being lymphocytes.PR requires two for 2+months.≥50%decrease in peripheral blood lymphocyte count from the pretreatment baseline value.≥ 50%reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions.≥ 50%reduction in size of liver and/or spleen noting the maximal distance below the respective costal margins of palpable hepatosplenomegaly during rest.Neutrophils>1500/ul or50%improvement over baseline. Platelets>100,000/ul or50%increase over baseline. Hemoglobin>11.0 gm/dl or50%increase over baseline without transfusions

2. Number of Participants With Dose-Limiting Toxicities [1 Month]

   The maximum tolerated dose is the dose level below the lowest dose that induces dose-limiting toxicity 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. Dose-limiting toxicity will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria. Hematologic: ANC ≤ 0.3 x 109/L or platelet count < 10 x 109/L Other nonhematologic: ≥grade 3 as per NCI Common Terminology Criteria for Adverse Events v3.0 except for fatigue, hyperlipidemia, and hyperglycemia.

3. Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab. [Up to 12 months past final treatment]

   The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group. Below is the number of patients that experienced a grade 3+ Adverse event that was at least possibly related to Treatment.

Secondary Outcome Measures

1. Survival Time [up to 5 years]

   Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier

2. Progression-free Survival [up to 5 years]

   Progression-free survival time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier

3. Duration of Response [up to 5 years]

   Duration of response is defined for all evaluable patients who have achieved a clinical response as the date at which the patient's objective status is first noted to be a Complete Response or Partial Response to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier

4. Time to Subsequent Therapy [up to 5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 120 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion

• Diagnosis of CLL manifested by minimum threshold peripheral lymphocyte count of > 5 x 10^9/L (CLL variant) OR palpable adenopathy >= 1cm or clinically palpable splenomegaly (SLL variant); AND immunophenotypic demonstrations of a population of B lymphocytes (as defined by CD19+) which are monoclonal (by light chain exclusion)

• CLL will be diagnosed if these cells have >= 3 of the following characteristics: CD5+, CD23+, dim surface light chain expression, dim surface CD20 expression, AND FISH analysis is negative for IGH/CCND1 and/or immunostaining is negative for cyclin D1 expression to exclude mantle cell lymphoma Previous treatment for CLL Progressive disease: symptomatic CLL (weight loss>10% within 6 months, extreme fatigue, fevers>38.5 C, drenching night sweats without evidence of infection) OR evidence of progressive bone marrow failure (hemoglobin<11g/dL, platelet count<100 x 10^9/L) OR massive (>6 cm below left costal margin) or progressive palpable splenomegaly OR massive (>10 cm) or measurable and progressive lymphadenopathy

• Please contact study investigator and/or consult protocol document for specific details on laboratory criteria CD52 expression by CLL cells Willing to provide mandatory biospecimen samples for research studies as required by the protocol Negative serum pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Willingness to return to the enrolling institution for follow-up

• ECOG Performance Status (PS) 0, 1, or 2--Exceptions: Grade 3 allowed if caused by CLL and not other co-morbidities Provide informed written consent Life expectancy >= 3 months

Exclusion

• Any of the following comorbid conditions: NYHA class III-IV heart disease, recent myocardial infarction (< 6 months prior to registration), uncontrolled infection, infection with the human immunodeficiency virus (HIV/AIDS), serological evidence of active hepatitis B infection (HBsAg or HBeAg positive) or positive hepatitis C serology, as further severe immunosuppression with this regimen may occur

• Evidence of active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia Other active primary malignancy requiring treatment or that limits survival to =< 2 years Any major surgery =< 4 weeks prior to registration Concurrent investigational drug therapy Any of the following: pregnant women,nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, abstinence, etc.)

• Concomitant use of the following CYP3A4 strong inhibitors: Clarithromycin, Nefazodone, Telithromycin, Aprepitant, Indinavir, Nelfinavir, Diltiazem, Borisonazole, Itrazonazole, Ritonavir, Erythromycin, Ketoconazole, Saquinavir, Fluconazole (may be used if drug levels can be monitored)

• Patients with any known bleeding diathesis (any congenital bleeding disorder that affects platelet function and/or coagulation including von Willebrand's Disease)

• Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 88% or less at rest on room air Receiving anticoagulant therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
2	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Study Chair: Clive S. Zent, M.D., Mayo Clinic
• Principal Investigator: Jose F. Leis, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00935792
• Other Study ID Numbers: MC088C; MC088C; NCI-2009-00935; 08-008775
• First Posted: Jul 9, 2009
• Last Update Posted: Sep 26, 2017
• Last Verified: Jan 1, 2016

• Keywords provided by Mayo Clinic: hematopoietic cancer; lymphoid cancer
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Antineoplastic Agents, Immunological; Alemtuzumab; Everolimus; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2	Phase 2, Dose Level 1
Arm/Group Description	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Period Title: Overall Study
STARTED	7	9	12
COMPLETED	6	6	12
NOT COMPLETED	1	3	0

Baseline Characteristics

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2	Phase 2, Dose Level 1	Total
Arm/Group Description	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Total of all reporting groups
Overall Participants	6	6	12	24
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	72.5	73	71	72
Sex: Female, Male (Count of Participants)
Female	4 66.7%	4 66.7%	4 33.3%	12 50%
Male	2 33.3%	2 33.3%	8 66.7%	12 50%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	12 100%	24 100%
Previouse number of regimens (regimens) [Median (Full Range) ]
Median (Full Range) [regimens]	2	3.5	3	3

Outcome Measures

1. Primary Outcome

Title	Clinical Response (Complete or Partial Remission)
Description	CR requires all of the following for a period of at least 2months:Absence of lymphadenopathy.No hepatomegaly or splenomegaly.Absence of constitutional symptoms.• Neutrophils>1500/ul•Platelets>100,000/ul • Hemoglobin >11.0gm/dl• Peripheral blood lymphocytes <4000/uLBonemarrow. normocellular with<30%of nucleated cells being lymphocytes.PR requires two for 2+months.≥50%decrease in peripheral blood lymphocyte count from the pretreatment baseline value.≥ 50%reduction in the sum of the products of the maximal perpendicular diameters of the largest measured node or nodal masses in the right and left cervical, axillary, and inguinal lymph node regions.≥ 50%reduction in size of liver and/or spleen noting the maximal distance below the respective costal margins of palpable hepatosplenomegaly during rest.Neutrophils>1500/ul or50%improvement over baseline. Platelets>100,000/ul or50%increase over baseline. Hemoglobin>11.0 gm/dl or50%increase over baseline without transfusions
Time Frame	After 2 courses of treatment

Outcome Measure Data

Analysis Population Description

All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response.

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2	Phase 2, Dose Level 1
Arm/Group Description	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	6	6	12
Complete Response	0 0%	1 16.7%	0 0%
Partial Response	3 50%	1 16.7%	3 25%

2. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicities
Description	The maximum tolerated dose is the dose level below the lowest dose that induces dose-limiting toxicity 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. Dose-limiting toxicity will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria. Hematologic: ANC ≤ 0.3 x 109/L or platelet count < 10 x 109/L Other nonhematologic: ≥grade 3 as per NCI Common Terminology Criteria for Adverse Events v3.0 except for fatigue, hyperlipidemia, and hyperglycemia.
Time Frame	1 Month

Outcome Measure Data

Analysis Population Description

All phase 1 patients are evaluable

Arm/Group Title	Phase 1, Dose Level 1	Phase 1, Dose Level 2
Arm/Group Description	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.	Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	6	6
Number [participants with DLTs]	1 16.7%	2 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 1, Dose Level 1, Phase 1, Dose Level 2
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		Estimated maximum tolerated dose was 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.

3. Primary Outcome

Title	Test the Safety and Tolerability of the Combination of Everolimus and Alemtuzumab.
Description	The number and severity of all adverse events will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group. Below is the number of patients that experienced a grade 3+ Adverse event that was at least possibly related to Treatment.
Time Frame	Up to 12 months past final treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Evaluable Patients
Arm/Group Description	Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	24
Number [participants]	16 266.7%

4. Secondary Outcome

Title	Survival Time
Description	Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Evaluable Patients
Arm/Group Description	Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	24
Median (95% Confidence Interval) [Months]	29.5

5. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival time is defined as the time from registration to progression or death due to any cause. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Evaluable Patients
Arm/Group Description	Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	24
Median (95% Confidence Interval) [Months]	4.9

6. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined for all evaluable patients who have achieved a clinical response as the date at which the patient's objective status is first noted to be a Complete Response or Partial Response to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

These are 8 patients with verified complete or partial responses(used in primary outcome measure) as well as 2 non verified partial responses.

Arm/Group Title	All Evaluable Patients
Arm/Group Description	Patients are only evaluable for duration of response when they have already been noted as a complete response or partial response.
Measure Participants	10
Median (95% Confidence Interval) [Months]	4.6

7. Secondary Outcome

Title	Time to Subsequent Therapy
Time Frame	up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Evaluable Patients
Arm/Group Description	Patients receive oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
Measure Participants	24
Median (95% Confidence Interval) [Months]	13.9

Adverse Events

Arm/Group Title	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 2, Dose Level 1
Arm/Group Description	Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.		Patients receive 5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.		Patients receive 2.5mg of oral everolimus thrice weekly for 9 weeks and alemtuzumab subcutaneously thrice weekly for 8 weeks.
All Cause Mortality
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 2, Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 2, Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		1/9 (11.1%)		0/12 (0%)
Vascular disorders
Thrombosis	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Phase 1, Dose Level 1		Phase 1, Dose Level 2		Phase 2, Dose Level 1
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/7 (100%)		8/9 (88.9%)		12/12 (100%)
Blood and lymphatic system disorders
Febrile neutropenia	1/7 (14.3%)	1	2/9 (22.2%)	2	2/12 (16.7%)	2
Hemoglobin decreased	5/7 (71.4%)	7	3/9 (33.3%)	4	1/12 (8.3%)	2
Hemolysis	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Ear and labyrinth disorders
Hearing loss	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Gastrointestinal disorders
Abdominal pain	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	2
Diarrhea	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Ear, nose and throat examination abnormal	1/7 (14.3%)	1	0/9 (0%)	0	2/12 (16.7%)	2
Gastrointestinal disorder	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Oral hemorrhage	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Upper gastrointestinal hemorrhage	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
General disorders
Chills	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Fatigue	4/7 (57.1%)	4	3/9 (33.3%)	3	2/12 (16.7%)	2
Fever	4/7 (57.1%)	8	2/9 (22.2%)	2	4/12 (33.3%)	4
Immune system disorders
Hypersensitivity	0/7 (0%)	0	2/9 (22.2%)	2	0/12 (0%)	0
Infections and infestations
Bladder infection	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Bronchitis	2/7 (28.6%)	3	0/9 (0%)	0	3/12 (25%)	3
Colitis, infectious (e.g., Clostridium difficile)	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Esophageal infection	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Mucosal infection	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Opportunistic infection	1/7 (14.3%)	2	1/9 (11.1%)	1	4/12 (33.3%)	6
Pharyngitis	1/7 (14.3%)	2	1/9 (11.1%)	1	0/12 (0%)	0
Pneumonia	1/7 (14.3%)	3	1/9 (11.1%)	1	2/12 (16.7%)	2
Sepsis	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Sinusitis	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Skin infection	2/7 (28.6%)	3	0/9 (0%)	0	1/12 (8.3%)	1
Upper respiratory infection	4/7 (57.1%)	5	2/9 (22.2%)	3	4/12 (33.3%)	4
Injury, poisoning and procedural complications
Fracture	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Investigations
Bilirubin increased	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Leukocyte count decreased	5/7 (71.4%)	7	8/9 (88.9%)	14	11/12 (91.7%)	28
Lymphocyte count decreased	1/7 (14.3%)	1	5/9 (55.6%)	12	11/12 (91.7%)	29
Neutrophil count decreased	5/7 (71.4%)	9	5/9 (55.6%)	9	7/12 (58.3%)	19
Platelet count decreased	5/7 (71.4%)	6	5/9 (55.6%)	6	5/12 (41.7%)	9
Metabolism and nutrition disorders
Anorexia	1/7 (14.3%)	1	1/9 (11.1%)	1	1/12 (8.3%)	1
Blood glucose increased	0/7 (0%)	0	1/9 (11.1%)	1	0/12 (0%)	0
Blood uric acid increased	0/7 (0%)	0	0/9 (0%)	0	2/12 (16.7%)	2
Dehydration	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Serum calcium increased	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	1
Serum triglycerides increased	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	3
Musculoskeletal and connective tissue disorders
Joint pain	1/7 (14.3%)	1	1/9 (11.1%)	1	0/12 (0%)	0
Nervous system disorders
Peripheral motor neuropathy	1/7 (14.3%)	2	0/9 (0%)	0	0/12 (0%)	0
Peripheral sensory neuropathy	1/7 (14.3%)	1	0/9 (0%)	0	0/12 (0%)	0
Psychiatric disorders
Psychosis	0/7 (0%)	0	0/9 (0%)	0	1/12 (8.3%)	2
Respiratory, thoracic and mediastinal disorders
Cough	1/7 (14.3%)	1	1/9 (11.1%)	1	0/12 (0%)	0
Dyspnea	2/7 (28.6%)	2	0/9 (0%)	0	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Rash desquamating	1/7 (14.3%)	1	2/9 (22.2%)	3	6/12 (50%)	10
Sweating	1/7 (14.3%)	1	0/9 (0%)	0	1/12 (8.3%)	2

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.