Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia

• Sponsor: Eastern Cooperative Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00046930
• Collaborator: National Cancer Institute (NCI) (NIH), Eli Lilly and Company (Industry), Kanisa Pharmaceuticals (Industry)
• Enrollment: 449
• Locations: 92
• Arms: 2
• Patients Per Site: 4.9

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar trihydrochloride, a modulator of multidrug resistance (MDR), may help daunorubicin and cytarabine kill more cancer cells by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or anemia.

PURPOSE: This randomized phase III trial is studying how well giving zosuquidar trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or anemia that has not responded to previous treatment.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndromes	Biological: filgrastim; Biological: sargramostim; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: zosuquidar trihydrochloride; Drug: Placebo	Phase 3

Detailed Description

OBJECTIVES:

• Compare the overall survival and progression-free survival of elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or without zosuquidar trihydrochloride.

• Compare the complete remission rate of patients treated with these regimens.

• Compare the toxicity of these regimens in these patients.

• Compare the systemic exposure of daunorubicin and cytarabine in patients treated with zosuquidar trihydrochloride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (60-69 years vs 70 years and over), disease (refractory anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]), and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

• Induction:

• Arm I: Patients receive daunorubicin via intravenous (IV) infusion over 10-15 minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also receive cytarabine IV continuously on days 1-7.

• Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also receive placebo IV over 6 hours on days 1-3.

Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) or IV daily until blood counts recover. Patients who have evidence of persistent AML are eligible to receive a second identical course of induction chemotherapy.

• Consolidation I (beginning within 8 weeks after documentation of complete remission [CR] or measurable remission [MR]): Patients who achieve a CR or MR receive cytarabine IV over 1 hour once or twice daily on days 1-6 and GM-CSF or G-CSF SC or IV beginning on day 7 and continuing until blood counts recover.

• Consolidation II: Patients who have maintained peripheral blood evidence of a remission receive daunorubicin, cytarabine, and zosuquidar trihydrochloride or placebo as in induction chemotherapy. Patients also receive GM-CSF or G-CSF SC or IV beginning on day 8 or after last cytarabine dose and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 450 patients (225 per treatment arm) accrued over 4.1 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 449 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Patients Greater Than 60 Years of Age With Newly Diagnosed Acute Myeloid Leukemia, Refractory Anemia With Excess Blasts in Transformation or High-Risk Refractory Anemia With Excess Blasts
• Study Start Date: Jul 1, 2002
• Actual Primary Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zosuquidar Induction treatment with daunorubicin, cytarabine and zosuquidar (details provided in Intervention section), followed by consolidation with Cytarabine (1500 mg/m2 every 12 hours for 6 days), then additional consolidation with the same regimen as received during induction.	Biological: filgrastim; 250 μg/m2/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; Other Names: Neupogen, recombinant-methionyl human granulocyte-colony stimulating factor, granulocyte colony-stimulating factor, r-metHuG-CSF ; Biological: sargramostim; 5 μg/kg/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; Other Names: Granulocyte-macrophage colony stimulating factor, rHu GM-CSF, Leukine, NSC # 617589 ; Drug: cytarabine; 100 mg/m²/day by continuous intravenous infusion for 7 days (days 1-7).; Other Names: Cytosar-U, Ara-C, Arabinosyl, cytosine arabinoside. ; Drug: daunorubicin hydrochloride; 45 mg/m²/day by 10 - 15 minute intravenous infusion for 3 days (days 1, 2, and 3).; Other Names: Daunomycin, Rubidomycin, Cerubidine. ; Drug: zosuquidar trihydrochloride; Zosuquidar 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3. The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3.; Other Names: Multi drug resistance modulator, MDR, LY335979
Active Comparator: Placebo Induction treatment with daunorubicin, cytarabine and placebo (details provided in Intervention section), followed by consolidation with Cytarabine (1500 mg/m2 every 12 hours for 6 days), then additional consolidation with the same regimen as received during induction.	Biological: filgrastim; 250 μg/m2/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; Other Names: Neupogen, recombinant-methionyl human granulocyte-colony stimulating factor, granulocyte colony-stimulating factor, r-metHuG-CSF ; Biological: sargramostim; 5 μg/kg/day by either intravenous or subcutaneous injection starting day 12, provided marrow aplasia is achieved, through recovery of absolute neutrophil count (ANC) to > 500 cells/μl, sustained for 3 consecutive days. The dose may be rounded to the nearest vial size.; Other Names: Granulocyte-macrophage colony stimulating factor, rHu GM-CSF, Leukine, NSC # 617589 ; Drug: cytarabine; 100 mg/m²/day by continuous intravenous infusion for 7 days (days 1-7).; Other Names: Cytosar-U, Ara-C, Arabinosyl, cytosine arabinoside. ; Drug: daunorubicin hydrochloride; 45 mg/m²/day by 10 - 15 minute intravenous infusion for 3 days (days 1, 2, and 3).; Other Names: Daunomycin, Rubidomycin, Cerubidine. ; Drug: Placebo; Placebo 550 mg/day by continuous intravenous infusion through a central venous catheter over approximately 6 hours on days 1, 2, and 3. The infusion will begin approximately one hour prior to daunorubicin on days 1, 2 and 3. Placebo consisted of a 1:1000 dilution of Infuvite, appropriately colored.; Other Names: Baxter Infuvite Adult

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter]

   Time from randomization to death. Patients alive at last follow-up were censored.

Secondary Outcome Measures

1. Progression-free Survival (PFS) [Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter]

   Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.

2. Response [Assessed at the end of induction]

   Number of eligible participants in each response category. Categories, based on peripheral blood counts and bone marrow aspirate and biopsy, include complete remission (CR), partial remission (PR), morphologic complete remission (MCR), and relapse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

One of the following disorders:

• Acute myeloid leukemia (AML), defined as >30% myeloblasts on the marrow aspirate or peripheral blood differential and any French-American-British (FAB) subtype except M3 (i.e., acute promyelocytic leukemia)

• Refractory anemia with excess blasts (RAEB), defined as 11-20% myeloblasts on bone marrow aspirate or peripheral blood differential, provided there are other criteria for high-risk disease

• Refractory anemia with excess blasts in transformation (RAEB-T), defined as 21-30% myeloblasts on bone marrow aspirate or peripheral blood differential

• Participants may have secondary AML

• Age greater than 60 years

• ECOG performance status of 0 to 3

• Total serum bilirubin < 3 mg/dL

• Serum creatinine < 2 mg/dL

• Cardiac ejection fraction of > 45%

Exclusion Criteria:

• Blastic transformation of chronic myelogenous leukemia

• CNS leukemia

• Prior chemotherapy for AML, with the exception of hydroxyurea

• For women: pregnant or breast feeding

• Other malignancy for which participant is currently receiving treatment

• Concurrent treatment with other colony-stimulating factors

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Mayo Clinic Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259
2	Aurora Presbyterian Hospital	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301
4	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado	United States	80933
5	Porter Adventist Hospital	Denver	Colorado	United States	80210
6	Presbyterian - St. Luke's Medical Center	Denver	Colorado	United States	80218
7	St. Joseph Hospital	Denver	Colorado	United States	80218
8	Rose Medical Center	Denver	Colorado	United States	80220
9	CCOP - Colorado Cancer Research Program, Incorporated	Denver	Colorado	United States	80224-2522
10	Swedish Medical Center	Englewood	Colorado	United States	80110
11	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
12	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado	United States	80502
13	St. Mary-Corwin Regional Medical Center	Pueblo	Colorado	United States	81004
14	North Suburban Medical Center	Thorton	Colorado	United States	80229
15	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610
16	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
17	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224-9980
18	Watson Clinic, LLC	Lakeland	Florida	United States	33805
19	H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Tampa	Florida	United States	33612
20	MBCCOP-Medical College of Georgia Cancer Center	Augusta	Georgia	United States	30912
21	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
22	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611
23	Rush University Medical Center	Chicago	Illinois	United States	60612
24	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
25	Evanston Northwestern Health Care - Evanston Hospital	Evanston	Illinois	United States	60201
26	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
27	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
28	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202
29	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana	United States	46202
30	McFarland Clinic, P.C.	Ames	Iowa	United States	50010
31	Siouxland Hematology-Oncology Associates	Sioux City	Iowa	United States	51101
32	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
33	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
34	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
35	Cancer Center of Kansas - Kingman	Kingman	Kansas	United States	67068
36	Southwest Medical Center	Liberal	Kansas	United States	67901
37	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
38	Pratt Cancer Center of Kansas	Pratt	Kansas	United States	67124
39	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67042
40	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
41	Associates in Womens Health	Wichita	Kansas	United States	67203
42	Cancer Center of Kansas, P.A.	Wichita	Kansas	United States	67208
43	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas	United States	67214
44	CCOP - Wichita	Wichita	Kansas	United States	67214
45	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
46	Wesley Medical Center	Wichita	Kansas	United States	67214
47	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
48	Tufts - New England Medical Center	Boston	Massachusetts	United States	02111
49	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
50	Baystate Regional Cancer Program at D'Amour Center for Cancer Care	Springfield	Massachusetts	United States	01199
51	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48100
52	St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
53	Borgess Medical Center	Kalamazooaa	Michigan	United States	49001
54	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
55	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
56	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
57	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
58	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
59	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
60	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55403
61	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota	United States	55422
62	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
63	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
64	Park Nicollet Clinic	St. Louis Park	Minnesota	United States	55416
65	United Hospital	St. Paul	Minnesota	United States	55102
66	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
67	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
68	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
69	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
70	Booker Cancer Center at Riverview Medical Center	Red Bank	New Jersey	United States	07701
71	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York	United States	10461
72	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
73	Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital	Greenville	North Carolina	United States	27858
74	Aultman Hospital Cancer Center at Aultman Health Foundation	Canton	Ohio	United States	44710
75	Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University	Cleveland	Ohio	United States	44106
76	MetroHealth's Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
77	St. Luke's Hospital Cancer Center	Bethlehem	Pennsylvania	United States	18015
78	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
79	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
80	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
81	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburg	Pennsylvania	United States	15213
82	Guthrie Medical Center - Sayre	Sayre	Pennsylvania	United States	18840
83	Hematology and Oncology Associates	Scranton	Pennsylvania	United States	18510
84	Geisinger Medical Group	State College	Pennsylvania	United States	16801
85	Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
86	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota	United States	57104
87	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
88	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
89	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
90	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
91	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
92	Rambam Medical Center	Haifa		Israel

Sponsors and Collaborators

• Eastern Cooperative Oncology Group
• National Cancer Institute (NCI)
• Eli Lilly and Company
• Kanisa Pharmaceuticals

Investigators

• Study Chair: Larry D. Cripe, MD, Indiana University Melvin and Bren Simon Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00046930
• Other Study ID Numbers: CDR0000257122; E3999; U10CA021115; NCT00046046
• First Posted: Jan 27, 2003
• Last Update Posted: Jun 26, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by Eastern Cooperative Oncology Group: adult acute monocytic leukemia (M5b); adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; de novo myelodysplastic syndromes; adult acute minimally differentiated myeloid leukemia (M0); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Cytarabine; Daunorubicin; Molgramostim; Lenograstim; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Zosuquidar	Placebo
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar	Induction treatment with daunorubicin, cytarabine and placebo
Period Title: Overall Study
STARTED	224	225
COMPLETED	212	221
NOT COMPLETED	12	4

Baseline Characteristics

Arm/Group Title	Zosuquidar	Placebo	Total
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar	Induction treatment with daunorubicin, cytarabine and placebo	Total of all reporting groups
Overall Participants	212	221	433
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.4 (5.5)	69.2 (5.3)	69.3 (5.4)
Sex: Female, Male (Count of Participants)
Female	103 48.6%	85 38.5%	188 43.4%
Male	109 51.4%	136 61.5%	245 56.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Time from randomization to death. Patients alive at last follow-up were censored.
Time Frame	Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter

Outcome Measure Data

Analysis Population Description

Eligible participants, as randomized

Arm/Group Title	Zosuquidar	Placebo
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar	Induction treatment with daunorubicin, cytarabine and placebo
Measure Participants	212	221
Median (95% Confidence Interval) [Months]	7.23	9.43

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zosuquidar, Placebo
	Comments	The study was designed to have 80% power to detect a non-proportional hazards difference in OS at the one-sided 0.025 significance level of 30.2% vs 39.6%, 12.8% vs 27.1% and 7.0% vs 14.0% at 1 years, 2 years, and full information for zosuquidar and placebo, respectively.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Log Rank
	Comments	Stratified on age (< 70 vs. >=70) and type of leukemia (de novo AML, secondary RAEB-t, or secondary RAEB AML)

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
Time Frame	Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter

Outcome Measure Data

Analysis Population Description

Eligible participants, as randomized. Patients who had neither documented progression nor death within 3 months of registration without disease evaluation were excluded.

Arm/Group Title	Zosuquidar	Placebo
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar	Induction treatment with daunorubicin, cytarabine and placebo
Measure Participants	202	211
Median (95% Confidence Interval) [Months]	3.02	2.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zosuquidar, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	Log Rank
	Comments	Stratified on age and type of leukemia

3. Secondary Outcome

Title	Response
Description	Number of eligible participants in each response category. Categories, based on peripheral blood counts and bone marrow aspirate and biopsy, include complete remission (CR), partial remission (PR), morphologic complete remission (MCR), and relapse.
Time Frame	Assessed at the end of induction

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zosuquidar	Placebo
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar	Induction treatment with daunorubicin, cytarabine and placebo
Measure Participants	212	221
Complete Remission	98 46.2%	96 43.4%
Morphologic Complete Remission	12 5.7%	12 5.4%
Partial Remission	2 0.9%	0 0%
Relapse	67 31.6%	90 40.7%
Unevaluable	33 15.6%	23 10.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zosuquidar, Placebo
	Comments	Test of difference in the CR (complete remission) rate between the arms.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.617
	Comments	Test was stratified on age and type of leukemia.
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Zosuquidar/Placebo

Adverse Events

Time Frame	Assessed every day until discharged from hospital, then twice weekly until ANC and platelets returned to normal levels. Complete blood counts were obtained monthly for 12 months, then every other month for 12 months.
Adverse Event Reporting Description	In addition to lab assessed as above, clinical events were reported via case report forms at the end of Induction, Consolidation I, and Consolidation II. After the end of treatment, forms were collected every 3 months for 2 years, then every 6 months for 3 years. CTCv2 reports were electronically mapped to CTCAE3.
Arm/Group Title	Zosuquidar Induction		Placebo Induction		Consolidation I		Zosuquidar Consolidation II		Placebo Consolidation II
Arm/Group Description	Induction treatment with daunorubicin, cytarabine and zosuquidar		Induction treatment with daunorubicin, cytarabine and placebo		Cytarabine 1500 mg/m2 days 1-6		Consolidation with Daunorubicin, Cytarabine and Zosuquidar		Consolidation with Daunorubicin, Cytarabine and Placebo
All Cause Mortality
	Zosuquidar Induction		Placebo Induction		Consolidation I		Zosuquidar Consolidation II		Placebo Consolidation II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Zosuquidar Induction		Placebo Induction		Consolidation I		Zosuquidar Consolidation II		Placebo Consolidation II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	216/219 (98.6%)		218/222 (98.2%)		173/180 (96.1%)		59/59 (100%)		69/70 (98.6%)
Blood and lymphatic system disorders
Bone Marrow Hypocellularity	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Anemia	160/219 (73.1%)		152/222 (68.5%)		94/180 (52.2%)		32/59 (54.2%)		37/70 (52.9%)
Hemolysis	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Leukopenia	205/219 (93.6%)		211/222 (95%)		167/180 (92.8%)		58/59 (98.3%)		66/70 (94.3%)
Lymphopenia	3/219 (1.4%)		5/222 (2.3%)		3/180 (1.7%)		1/59 (1.7%)		2/70 (2.9%)
Neutropenia	200/219 (91.3%)		202/222 (91%)		153/180 (85%)		48/59 (81.4%)		61/70 (87.1%)
Thrombocytopenia	210/219 (95.9%)		214/222 (96.4%)		169/180 (93.9%)		48/59 (81.4%)		61/70 (87.1%)
Transfusion: Platelets	20/219 (9.1%)		23/222 (10.4%)		20/180 (11.1%)		5/59 (8.5%)		10/70 (14.3%)
Transfusion: Peripheral Red Blood Cells	18/219 (8.2%)		18/222 (8.1%)		15/180 (8.3%)		4/59 (6.8%)		8/70 (11.4%)
Hematologic - Other	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Disseminated Intravascular Coagulation	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Thrombotic Microangiopathy	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Hemorrhage, GI, Hematemesis	1/219 (0.5%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		1/70 (1.4%)
Hemorrhage, GU, Hematuria	3/219 (1.4%)		3/222 (1.4%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Hemorrhage, Upper Respiratory, Hemoptysis	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hemorrhage Associated with Surgery	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hemorrhage, GI, Melena	5/219 (2.3%)		4/222 (1.8%)		0/180 (0%)		0/59 (0%)		3/70 (4.3%)
Petechiae	7/219 (3.2%)		13/222 (5.9%)		8/180 (4.4%)		0/59 (0%)		4/70 (5.7%)
Hemorrhage, GI, Rectum	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hemorrhage, GU, Vagina	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Lymphatics, Other	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Cardiac disorders
Conduction Abnormality	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Dysrhythmia	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Sinus Bradycardia	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Sinus Tachycardia	4/219 (1.8%)		5/222 (2.3%)		2/180 (1.1%)		0/59 (0%)		0/70 (0%)
Supraventricular Arrhythmia	16/219 (7.3%)		8/222 (3.6%)		4/180 (2.2%)		0/59 (0%)		0/70 (0%)
Ventricular Arrhythmia	0/219 (0%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Arrhythmia - Other	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Cardiac Ischemia	4/219 (1.8%)		2/222 (0.9%)		1/180 (0.6%)		1/59 (1.7%)		0/70 (0%)
Cardiac - Left Ventricular Dysfunction	6/219 (2.7%)		8/222 (3.6%)		3/180 (1.7%)		2/59 (3.4%)		1/70 (1.4%)
Cardiac Troponin I Increased	2/219 (0.9%)		2/222 (0.9%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Cardiac Troponin T Increased	2/219 (0.9%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Acute Vascular Leak Syndrome	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypertension	3/219 (1.4%)		7/222 (3.2%)		0/180 (0%)		1/59 (1.7%)		0/70 (0%)
Edema	6/219 (2.7%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypotension	16/219 (7.3%)		9/222 (4.1%)		2/180 (1.1%)		1/59 (1.7%)		1/70 (1.4%)
Cardiac, Other	1/219 (0.5%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Endocrine disorders
Neuroendocrine: ADH Secretion Abnormality	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Eye disorders
Conjunctivitis	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Vision - Blurred	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Nystagmus	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Keratitis	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Gastrointestinal disorders
Anorexia	29/219 (13.2%)		20/222 (9%)		5/180 (2.8%)		3/59 (5.1%)		4/70 (5.7%)
Ascites	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Colitis	5/219 (2.3%)		3/222 (1.4%)		3/180 (1.7%)		1/59 (1.7%)		2/70 (2.9%)
Constipation	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Dehydration	4/219 (1.8%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		1/70 (1.4%)
Heartburn/Dyspepsia	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Dysphagia	10/219 (4.6%)		2/222 (0.9%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Ulcer, Gastric	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Nausea	18/219 (8.2%)		12/222 (5.4%)		3/180 (1.7%)		1/59 (1.7%)		1/70 (1.4%)
Pancreatitis	2/219 (0.9%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Stomatitis	19/219 (8.7%)		11/222 (5%)		3/180 (1.7%)		3/59 (5.1%)		2/70 (2.9%)
Typhlitis	3/219 (1.4%)		2/222 (0.9%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Vomiting	6/219 (2.7%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Diarrhea w/o Prior Colostomy	16/219 (7.3%)		13/222 (5.9%)		5/180 (2.8%)		4/59 (6.8%)		4/70 (5.7%)
Diarrhea w/Colostomy	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
GI, Other	4/219 (1.8%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Pain, Abdomen	8/219 (3.7%)		5/222 (2.3%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Pain, Rectum	1/219 (0.5%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
General disorders
Fatigue	38/219 (17.4%)		22/222 (9.9%)		8/180 (4.4%)		4/59 (6.8%)		2/70 (2.9%)
Fever w/o neutropenia	1/219 (0.5%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Rigors/Chills	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Constitutional, Other	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Pain, Other	3/219 (1.4%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hepatobiliary disorders
Liver Dysfunction/Failure	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hepatic, Other	0/219 (0%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		1/70 (1.4%)
Infections and infestations
Infection, Catheter Related	5/219 (2.3%)		8/222 (3.6%)		2/180 (1.1%)		2/59 (3.4%)		3/70 (4.3%)
Febrile Neutropenia	93/219 (42.5%)		82/222 (36.9%)		42/180 (23.3%)		12/59 (20.3%)		15/70 (21.4%)
Infection w/ Grade 3 or 4 Neutropenia	119/219 (54.3%)		121/222 (54.5%)		57/180 (31.7%)		29/59 (49.2%)		26/70 (37.1%)
Infection w/ Unknown ANC	1/219 (0.5%)		3/222 (1.4%)		2/180 (1.1%)		0/59 (0%)		0/70 (0%)
Infection without Neutropenia	8/219 (3.7%)		7/222 (3.2%)		17/180 (9.4%)		3/59 (5.1%)		4/70 (5.7%)
Infection, Other	2/219 (0.9%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Injury, poisoning and procedural complications
Hemorrhage, Other	12/219 (5.5%)		3/222 (1.4%)		4/180 (2.2%)		0/59 (0%)		3/70 (4.3%)
Investigations
Fibrinogen Decreased	0/219 (0%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Prolonged Partial Thromboplastin Time	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
PT (INR) Increased	1/219 (0.5%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Alkaline Phosphatase Increased	2/219 (0.9%)		4/222 (1.8%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Bilirubin Increased	36/219 (16.4%)		31/222 (14%)		2/180 (1.1%)		4/59 (6.8%)		1/70 (1.4%)
Gamma-glutamyl Transpeptidase (GGT) Increased	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypoalbuminemia	1/219 (0.5%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
ALT, SGPT Increased	5/219 (2.3%)		8/222 (3.6%)		2/180 (1.1%)		0/59 (0%)		1/70 (1.4%)
AST, SGOT Increased	8/219 (3.7%)		11/222 (5%)		2/180 (1.1%)		0/59 (0%)		2/70 (2.9%)
Acidosis	1/219 (0.5%)		3/222 (1.4%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Alkalosis	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Amylase Increased	2/219 (0.9%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Bicarbonate, Serum Decreased	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hyperglycemia	7/219 (3.2%)		3/222 (1.4%)		2/180 (1.1%)		0/59 (0%)		0/70 (0%)
Hyperkalemia	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypermagnesemia	3/219 (1.4%)		2/222 (0.9%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Hypernatremia	2/219 (0.9%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hyperuricemia	4/219 (1.8%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypocalcemia	17/219 (7.8%)		7/222 (3.2%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypoglycemia	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hypokalemia	16/219 (7.3%)		12/222 (5.4%)		3/180 (1.7%)		6/59 (10.2%)		1/70 (1.4%)
Hypomagnesemia	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Hyponatremia	11/219 (5%)		3/222 (1.4%)		3/180 (1.7%)		2/59 (3.4%)		1/70 (1.4%)
Hypophosphatemia	13/219 (5.9%)		4/222 (1.8%)		3/180 (1.7%)		2/59 (3.4%)		1/70 (1.4%)
Lipase Increased	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Ataxia	17/219 (7.8%)		2/222 (0.9%)		5/180 (2.8%)		2/59 (3.4%)		0/70 (0%)
Proteinuria	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Metabolism and nutrition disorders
Tumor Lysis Syndrome	6/219 (2.7%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Musculoskeletal and connective tissue disorders
Pain, Joint (Arthralgia)	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		1/70 (1.4%)
Pain, Bone	1/219 (0.5%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		1/70 (1.4%)
Pain, Muscle (Myalgia)	1/219 (0.5%)		1/222 (0.5%)		1/180 (0.6%)		0/59 (0%)		1/70 (1.4%)
Nervous system disorders
Muscle Weakness	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		1/59 (1.7%)		0/70 (0%)
Cerebrovascular Ischemia	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Confusion	18/219 (8.2%)		3/222 (1.4%)		1/180 (0.6%)		3/59 (5.1%)		0/70 (0%)
Psychosis (Hallucinations/Delusions)	24/219 (11%)		10/222 (4.5%)		2/180 (1.1%)		0/59 (0%)		0/70 (0%)
Somnolence/Depressed Level of Consciousness	8/219 (3.7%)		4/222 (1.8%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Dizziness/Lightheadedness	3/219 (1.4%)		0/222 (0%)		2/180 (1.1%)		0/59 (0%)		1/70 (1.4%)
Insomnia	1/219 (0.5%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Memory Impairment	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Mood Alteration: Anxiety/Agitation	3/219 (1.4%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Mood Alteration: Depression	1/219 (0.5%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Neuropathy, Motor	4/219 (1.8%)		2/222 (0.9%)		1/180 (0.6%)		1/59 (1.7%)		1/70 (1.4%)
Neuropathy, Sensory	1/219 (0.5%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Seizure	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Speech Impairment	4/219 (1.8%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Pyramidal Tract Dysfunction	0/219 (0%)		0/222 (0%)		0/180 (0%)		1/59 (1.7%)		0/70 (0%)
Syncope	0/219 (0%)		0/222 (0%)		2/180 (1.1%)		1/59 (1.7%)		0/70 (0%)
Tremor	5/219 (2.3%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Neurologic - Other	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Pain, Headache	1/219 (0.5%)		2/222 (0.9%)		2/180 (1.1%)		0/59 (0%)		0/70 (0%)
Renal and urinary disorders
Renal, Other - Dysuria	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Incontinence, Urinary	2/219 (0.9%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Renal Failure	4/219 (1.8%)		4/222 (1.8%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Urinary Frequency/Urgency	0/219 (0%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Urinary Retention	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Renal, Other	2/219 (0.9%)		1/222 (0.5%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, Upper Respiratory, Nose	12/219 (5.5%)		13/222 (5.9%)		2/180 (1.1%)		2/59 (3.4%)		4/70 (5.7%)
Pain, Pleura	0/219 (0%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Adult Respiratory Distress Syndrome (ARDS)	4/219 (1.8%)		0/222 (0%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Dyspnea	22/219 (10%)		21/222 (9.5%)		3/180 (1.7%)		1/59 (1.7%)		1/70 (1.4%)
Hypoxia	16/219 (7.3%)		12/222 (5.4%)		2/180 (1.1%)		1/59 (1.7%)		0/70 (0%)
Pneumonitis/Pulmonary Infiltrates	13/219 (5.9%)		11/222 (5%)		2/180 (1.1%)		0/59 (0%)		2/70 (2.9%)
Voice changes/Dysarthria	2/219 (0.9%)		2/222 (0.9%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Pulmonary, Other	4/219 (1.8%)		4/222 (1.8%)		0/180 (0%)		0/59 (0%)		0/70 (0%)
Skin and subcutaneous tissue disorders
Pruritis/itching	0/219 (0%)		0/222 (0%)		1/180 (0.6%)		0/59 (0%)		0/70 (0%)
Rash/Desquamation	10/219 (4.6%)		4/222 (1.8%)		2/180 (1.1%)		0/59 (0%)		1/70 (1.4%)
Wound, Infectious	1/219 (0.5%)		2/222 (0.9%)		2/180 (1.1%)		1/59 (1.7%)		0/70 (0%)
Vascular disorders
Thrombosis/Embolism	1/219 (0.5%)		2/222 (0.9%)		0/180 (0%)		1/59 (1.7%)		1/70 (1.4%)
Other (Not Including Serious) Adverse Events
	Zosuquidar Induction		Placebo Induction		Consolidation I		Zosuquidar Consolidation II		Placebo Consolidation II
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	218/219 (99.5%)		221/222 (99.5%)		180/180 (100%)		59/59 (100%)		70/70 (100%)
Blood and lymphatic system disorders
Anemia	210/219 (95.9%)		215/222 (96.8%)		179/180 (99.4%)		59/59 (100%)		70/70 (100%)
Leukopenia	171/219 (78.1%)		172/222 (77.5%)		152/180 (84.4%)		56/59 (94.9%)		69/70 (98.6%)
Neutropenia	134/219 (61.2%)		137/222 (61.7%)		116/180 (64.4%)		49/59 (83.1%)		57/70 (81.4%)
Thrombocytopenia	164/219 (74.9%)		183/222 (82.4%)		168/180 (93.3%)		57/59 (96.6%)		67/70 (95.7%)
Epistaxis	13/219 (5.9%)		18/222 (8.1%)		6/180 (3.3%)		4/59 (6.8%)		1/70 (1.4%)
Petechiae	21/219 (9.6%)		16/222 (7.2%)		10/180 (5.6%)		4/59 (6.8%)		2/70 (2.9%)
Cardiac disorders
Edema	34/219 (15.5%)		46/222 (20.7%)		17/180 (9.4%)		4/59 (6.8%)		7/70 (10%)
Hypotension	6/219 (2.7%)		5/222 (2.3%)		6/180 (3.3%)		1/59 (1.7%)		4/70 (5.7%)
Gastrointestinal disorders
Anorexia	52/219 (23.7%)		41/222 (18.5%)		29/180 (16.1%)		14/59 (23.7%)		11/70 (15.7%)
Constipation	25/219 (11.4%)		22/222 (9.9%)		11/180 (6.1%)		7/59 (11.9%)		8/70 (11.4%)
Heartburn/Dyspepsia	15/219 (6.8%)		13/222 (5.9%)		4/180 (2.2%)		2/59 (3.4%)		0/70 (0%)
Dysphagia	17/219 (7.8%)		10/222 (4.5%)		5/180 (2.8%)		1/59 (1.7%)		2/70 (2.9%)
Nausea	89/219 (40.6%)		88/222 (39.6%)		41/180 (22.8%)		17/59 (28.8%)		24/70 (34.3%)
Stomatitis	68/219 (31.1%)		61/222 (27.5%)		29/180 (16.1%)		14/59 (23.7%)		9/70 (12.9%)
Taste Disturbance	21/219 (9.6%)		16/222 (7.2%)		7/180 (3.9%)		4/59 (6.8%)		2/70 (2.9%)
Vomiting	56/219 (25.6%)		39/222 (17.6%)		16/180 (8.9%)		9/59 (15.3%)		8/70 (11.4%)
Diarrhea w/o Prior Colostomy	107/219 (48.9%)		92/222 (41.4%)		37/180 (20.6%)		20/59 (33.9%)		17/70 (24.3%)
Pain, Abdomen	28/219 (12.8%)		17/222 (7.7%)		10/180 (5.6%)		4/59 (6.8%)		5/70 (7.1%)
General disorders
Fatigue	77/219 (35.2%)		79/222 (35.6%)		78/180 (43.3%)		18/59 (30.5%)		26/70 (37.1%)
Fever w/o neutropenia	8/219 (3.7%)		14/222 (6.3%)		12/180 (6.7%)		4/59 (6.8%)		0/70 (0%)
Rigors/Chills	29/219 (13.2%)		31/222 (14%)		22/180 (12.2%)		6/59 (10.2%)		14/70 (20%)
Sweating	8/219 (3.7%)		15/222 (6.8%)		4/180 (2.2%)		1/59 (1.7%)		3/70 (4.3%)
Weight Loss	15/219 (6.8%)		9/222 (4.1%)		10/180 (5.6%)		4/59 (6.8%)		3/70 (4.3%)
Investigations
Alkaline Phosphatase Increased	101/219 (46.1%)		95/222 (42.8%)		57/180 (31.7%)		17/59 (28.8%)		15/70 (21.4%)
Bilirubin Increased	117/219 (53.4%)		113/222 (50.9%)		61/180 (33.9%)		12/59 (20.3%)		14/70 (20%)
Hypoalbuminemia	13/219 (5.9%)		11/222 (5%)		6/180 (3.3%)		4/59 (6.8%)		3/70 (4.3%)
AST, SGOT Increased	97/219 (44.3%)		84/222 (37.8%)		42/180 (23.3%)		19/59 (32.2%)		7/70 (10%)
ALT, SGPT Increased	75/219 (34.2%)		92/222 (41.4%)		47/180 (26.1%)		20/59 (33.9%)		12/70 (17.1%)
Hyperglycemia	18/219 (8.2%)		11/222 (5%)		11/180 (6.1%)		6/59 (10.2%)		4/70 (5.7%)
Hypermagnesemia	35/219 (16%)		22/222 (9.9%)		14/180 (7.8%)		4/59 (6.8%)		3/70 (4.3%)
Hypocalcemia	23/219 (10.5%)		17/222 (7.7%)		9/180 (5%)		5/59 (8.5%)		3/70 (4.3%)
Hypomagnesemia	92/219 (42%)		82/222 (36.9%)		56/180 (31.1%)		28/59 (47.5%)		22/70 (31.4%)
Hyponatremia	20/219 (9.1%)		16/222 (7.2%)		6/180 (3.3%)		3/59 (5.1%)		1/70 (1.4%)
Creatinine Increased	78/219 (35.6%)		59/222 (26.6%)		23/180 (12.8%)		10/59 (16.9%)		7/70 (10%)
Musculoskeletal and connective tissue disorders
Pain, Joint (Arthralgia)	9/219 (4.1%)		1/222 (0.5%)		7/180 (3.9%)		0/59 (0%)		6/70 (8.6%)
Pain, Bone	7/219 (3.2%)		3/222 (1.4%)		8/180 (4.4%)		0/59 (0%)		4/70 (5.7%)
Pain, Muscle (Myalgia)	10/219 (4.6%)		9/222 (4.1%)		11/180 (6.1%)		2/59 (3.4%)		6/70 (8.6%)
Nervous system disorders
Ataxia	11/219 (5%)		4/222 (1.8%)		6/180 (3.3%)		2/59 (3.4%)		0/70 (0%)
Confusion	17/219 (7.8%)		8/222 (3.6%)		1/180 (0.6%)		1/59 (1.7%)		1/70 (1.4%)
Dizziness/Lightheadedness	19/219 (8.7%)		8/222 (3.6%)		12/180 (6.7%)		1/59 (1.7%)		4/70 (5.7%)
Tremor	29/219 (13.2%)		12/222 (5.4%)		3/180 (1.7%)		5/59 (8.5%)		3/70 (4.3%)
Pain, Headache	22/219 (10%)		30/222 (13.5%)		14/180 (7.8%)		3/59 (5.1%)		8/70 (11.4%)
Respiratory, thoracic and mediastinal disorders
Cough	16/219 (7.3%)		19/222 (8.6%)		6/180 (3.3%)		2/59 (3.4%)		5/70 (7.1%)
Dyspnea	18/219 (8.2%)		13/222 (5.9%)		7/180 (3.9%)		2/59 (3.4%)		6/70 (8.6%)
Skin and subcutaneous tissue disorders
Alopecia	63/219 (28.8%)		70/222 (31.5%)		74/180 (41.1%)		25/59 (42.4%)		26/70 (37.1%)
Flushing	4/219 (1.8%)		2/222 (0.9%)		5/180 (2.8%)		5/59 (8.5%)		1/70 (1.4%)
Pruritis/Itching	12/219 (5.5%)		11/222 (5%)		5/180 (2.8%)		1/59 (1.7%)		1/70 (1.4%)
Rash/Desquamation	48/219 (21.9%)		43/222 (19.4%)		31/180 (17.2%)		12/59 (20.3%)		9/70 (12.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.