Dasatinib Followed by Stem Cell Transplant in Treating Older Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01256398
• Collaborator: (none)
• Enrollment: 66
• Locations: 101
• Arm: 1
• Actual Duration (Months): 131.1
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II clinical trial studies how well dasatinib followed by stem cell transplant works in treating older patients with newly diagnosed acute lymphoblastic leukemia. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Monoclonal antibodies, such as alemtuzumab, may interfere with the ability of cancer cells to grow and spread. Giving more than one drug (combination chemotherapy) and giving dasatinib together with chemotherapy may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1	Biological: Alemtuzumab; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dasatinib; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Etoposide Phosphate; Biological: Filgrastim; Drug: Fludarabine Phosphate; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Melphalan; Drug: Mercaptopurine; Drug: Methotrexate; Biological: Pegfilgrastim; Other: Pharmacological Study; Drug: Tacrolimus; Drug: Vincristine Sulfate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Estimate the disease-free survival (DFS) and overall survival (OS) profiles in newly diagnosed patients 18 years or older who have Philadelphia chromosome positive (Ph+) (BCR/(v-abl Abelson murine leukemia viral oncogene homolog [ABL]+) acute lymphoblastic leukemia (ALL) receiving sequential dasatinib followed by allogeneic or autologous hematopoietic cell transplant (HCT) or chemotherapy followed by dasatinib maintenance.

SECONDARY OBJECTIVES:

1. Compare the OS and DFS profiles for each of the three cohorts to those from similar populations from other studies.

2. Determine the ability of dasatinib to produce or maintain a BCR/ABL-negative status, as judged by quantitative-polymerase chain reaction (Q-PCR) following sequential dasatinib, chemotherapy, and HCT.

3. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous HCT following dasatinib therapy and assess for residual Ph+ (BCR/ABL+) cells by Q-PCR.

4. Study the safety and efficacy of autologous HCT following therapy with dasatinib.

5. Study the safety and efficacy of reduced-intensity preparatory regimen followed by an allogeneic HCT following induction therapy with dasatinib.

6. Study the safety and efficacy of dasatinib maintenance administered after allogeneic or autologous HCT or chemotherapy.

7. Correlate plasma and cerebrospinal fluid (CSF) levels of dasatinib when given orally during induction.

OUTLINE: As of 8/21/2014, no new patients may be enrolled on E3903.

REMISSION INDUCTION THERAPY (RIT): Patients receive dasatinib orally (PO) daily continuously and dexamethasone PO or intravenously (IV) on days 1-7.

EARLY INTENSIFICATION THERAPY: Patients with bone marrow =< 20% blasts are assigned to cohort A and patients with bone marrow > 20% blasts are assigned to cohort B.

COHORT A: Patients receive dasatinib and dexamethasone as in RIT.

COHORT B: Patients receive dasatinib and dexamethasone as in RIT, and vincristine sulfate IV and daunorubicin hydrochloride IV on days 1, 8, and 15. Patients who do NOT achieve a complete response (CR) or CR with incomplete hematologic recovery based on bone marrow continue on to second induction therapy; patients who achieve a hematologic and morphologic CR continue on to CNS prophylaxis therapy.

SECOND INDUCTION THERAPY: Patients receive dasatinib and dexamethasone as in RIT, cyclophosphamide IV on day 1, daunorubicin hydrochloride IV and vincristine sulfate IV on days 1 and 8, and filgrastim subcutaneously (SC) beginning on day 9 and continuing for >= 7 days or one dose of pegfilgrastim on day 9.

CNS PROPHYLAXIS THERAPY: Patients receive dasatinib PO daily continuously during CNS prophylaxis therapy; methotrexate intrathecally (IT), vincristine sulfate IV, and methotrexate IV over 3 hours on days 1, 15, and 29; methotrexate PO every 6 hours for a total of 4 doses each on days 1-2, 15-16, and 29-30; leucovorin calcium IV on days 2, 16, and 30; and leucovorin PO calcium every 6 hours for a total of 8 doses each on days 3-4, 17-18, and 31-32.

TRANSPLANTATION OR ALTERNATIVE CHEMOTHERAPY AND MAINTENANCE THERAPY: Patients aged 50-70 years with an HLA-matched related or unrelated donor are assigned to allogeneic transplantation, patients aged 50-70 years without an HLA-matched related or unrelated donor are assigned to autologous transplantation, and patients aged > 70 years or who are not transplantation candidates are assigned to alternative chemotherapy.

ALLOGENEIC TRANSPLANTATION: Patients receive fludarabine phosphate IV over 30 minutes and alemtuzumab IV over 30 minutes on days -7 through -3 and melphalan IV over 30 minutes on day -2. Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients then receive filgrastim SC beginning on day 1 and continuing until count recovery and tacrolimus IV or PO beginning on day -2 and beginning to taper on day 100 (for matched related donors) or day 180 (for mismatched related or unrelated donors). Beginning on day 30, patients receive dasatinib PO daily as maintenance therapy. Treatment continues for >= 12 months in the absence of disease progression.

AUTOLOGOUS TRANSPLANTATION:

MOBILIZATION: Patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until peripheral blood stem cell collection is complete or WBC > 50,000/μL.

LEUKAPHERESIS: Patients undergo leukapheresis beginning when WBC > 10,000/μL for a target collection of >= 5 x 10^6 CD34+ cells/kg. After completion of stem cell collection, patients receive dasatinib PO twice daily until 3 days before transplantation.

TRANSPLANTATION: Beginning >= 4 weeks after recovery from toxicity related to previous treatment, patients receive melphalan IV over 30 minutes on days -2 and -1. Patients undergo autologous PBSCT on day 0. Patients then receive filgrastim SC beginning on day 0 and continuing until count recovery.

MAINTENANCE THERAPY: Beginning on day 30, patients receive dasatinib PO once daily. Treatment continues for >= 12 months in the absence of disease progression.

ALTERNATIVE CHEMOTHERAPY: Beginning 3-10 days after completion of CNS prophylaxis therapy, patients receive etoposide phosphate IV continuously on days 1-4, high-dose cytarabine IV over 2 hours every 12 hours for a total of 8 doses on days 1-4, and filgrastim SC once or twice daily beginning on day 14 and continuing until count recovery.

MAINTENANCE THERAPY: Patients receive dasatinib PO once daily beginning on day 30. Patients also receive vincristine sulfate IV every 4 weeks, dexamethasone for 5 days every 4 weeks, mercaptopurine PO once daily, and methotrexate PO once weekly. Treatment continues for >= 12 months in the absence of disease progression.

NOTE: Patients with CNS leukemia or testicular disease may receive additional treatment.

After completion of study treatment, patients are followed up every month for 1 year, every 3 months for 2 years, every 6 months for 2 years, and every year for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Dasatinib (Sprycel&#174;) (NSC #732517) as Primary Therapy Followed by Transplantation for Adults &gt;/= 18 Years With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by CALGB, ECOG and SWOG
• Actual Study Start Date: Dec 14, 2010
• Actual Primary Completion Date: Nov 14, 2017
• Actual Study Completion Date: Nov 15, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (chemotherapy, transplant) See Detailed Description

Biological: Alemtuzumab; Given IV; Other Names: Anti-CD52 Monoclonal Antibody Campath Campath-1H LDP-03 Lemtrada MabCampath Monoclonal Antibody Campath-1H ; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo peripheral blood allogeneic HCT; Other Names: Allogeneic Allogeneic Hematopoietic Cell Transplantation Allogeneic Stem Cell Transplantation HSC HSCT Stem Cell Transplantation, Allogeneic ; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo peripheral blood autologous HCT; Other Names: AHSCT Autologous Autologous Hematopoietic Cell Transplantation Autologous Stem Cell Transplant Autologous Stem Cell Transplantation Stem Cell Transplantation, Autologous ; Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Dasatinib; Given PO; Other Names: BMS-354825 Dasatinib Hydrate Dasatinib Monohydrate Sprycel ; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem ; Drug: Dexamethasone; Given PO or IV; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycadron Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decadron DP 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 Dexamethasone Intensol Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Dxevo Fluorodelta Fortecortin Gammacorten Hemady Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex TaperDex Visumetazone ZoDex ; Drug: Etoposide Phosphate; Given IV; Other Names: Etopophos ; Biological: Filgrastim; Given SC; Other Names: Filgrastim-aafi G-CSF Neupogen Nivestym r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tevagrastim ; Drug: Fludarabine Phosphate; Given IV; Other Names: 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 ; Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation; Undergo peripheral blood autologous or allogeneic HCT; Other Names: in vitro-treated PBPC transplantation in vitro-treated peripheral blood progenitor cell transplantation ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leucovorin Calcium; Given IV or PO; Other Names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin ; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Drug: Mercaptopurine; Given PO; Other Names: 3H-Purine-6-thiol 6 MP 6 Thiohypoxanthine 6 Thiopurine 6-Mercaptopurine 6-Mercaptopurine Monohydrate 6-MP 6-Purinethiol 6-Thiopurine 6-Thioxopurine 6H-Purine-6-thione, 1,7-dihydro- (9CI) 7-Mercapto-1,3,4,6-tetrazaindene Alti-Mercaptopurine Azathiopurine Bw 57-323H Flocofil Ismipur Leukerin Leupurin Mercaleukim Mercaleukin Mercaptina Mercaptopurinum Mercapurin Mern NCI-C04886 Puri-Nethol Purimethol Purine, 6-mercapto- Purine-6-thiol (8CI) Purine-6-thiol, monohydrate Purinethiol Purinethol U-4748 WR-2785 ; Drug: Methotrexate; Given IT, IV, or PO; Other Names: Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 ; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01 filgrastim-SD/01 Fulphila HSP-130 Jinyouli Neulasta Neulastim Nyvepria PEG-filgrastim Pegcyte Pegfilgrastim Biosimilar HSP-130 Pegfilgrastim Biosimilar Nyvepria Pegfilgrastim Biosimilar Pegcyte Pegfilgrastim Biosimilar PF-06881894 Pegfilgrastim Biosimilar Udenyca Pegfilgrastim Biosimilar Ziextenzo pegfilgrastim-apgf pegfilgrastim-bmez pegfilgrastim-cbqv Pegfilgrastim-jmdb PF-06881894 SD-01 SD-01 sustained duration G-CSF Udenyca Ziextenzo ; Other: Pharmacological Study; Correlative studies; Drug: Tacrolimus; Given IV or PO; Other Names: FK 506 Fujimycin Hecoria Prograf Protopic ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause [At 3 years after CR]

   Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.

Secondary Outcome Measures

1. Probability of Being BCR-ABL Negative in the Bone Marrow and Peripheral Blood at the Completion of the CNS Prophylaxis Course (Restricted to Those Patients Achieving a CR) [Up to 10 years]

   Proportions will be estimated based on the combined and individual cohorts.

2. Feasibility of Maintenance Therapy in This Patient Population (Restricted to Those Patients Achieving a CR) [Up to 10 years]

   Proportions will be estimated based on the combined and individual cohorts.

3. OS [Up to 10 years]

   Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.

4. DFS [From the date of first induction CR to relapse, or death due to any cause, with patients last known to be alive and disease-free censored at the date of last contact, assessed up to 10 years]

   Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.

5. Response [Up to 10 years]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Unequivocal histologic diagnosis of ALL

• Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive status by molecular analysis (Q-PCR or fluorescent in situ hybridization [FISH]) in a Cruise Lines International Association (CLIA)-approved laboratory

• No prior therapy except up to one week of corticosteroids and/or hydroxyurea to enable time for the detection of t(9;22)(q34;q11) or BCR/ABL

• Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of dasatinib to allow complete clearance of drug and its principal metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry

• Left ventricular ejection fraction >= lower limit of institutional normal

• No myocardial infarction within 6 months

• No ventricular tachyarrhythmia within 6 months

• No major conduction abnormality (unless a cardiac pacemaker is present)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
2	The Medical Center of Aurora	Aurora	Colorado	United States	80012
3	Boulder Community Hospital	Boulder	Colorado	United States	80301
4	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
5	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
6	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
7	Porter Adventist Hospital	Denver	Colorado	United States	80210
8	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
9	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
10	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
11	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
12	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
13	Rose Medical Center	Denver	Colorado	United States	80220
14	Western States Cancer Research NCORP	Denver	Colorado	United States	80222
15	Mercy Medical Center	Durango	Colorado	United States	81301
16	Mountain Blue Cancer Care Center - Swedish	Englewood	Colorado	United States	80113
17	Swedish Medical Center	Englewood	Colorado	United States	80113
18	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
19	North Colorado Medical Center	Greeley	Colorado	United States	80631
20	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
21	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
22	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
23	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
24	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
25	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
26	Longmont United Hospital	Longmont	Colorado	United States	80501
27	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
28	McKee Medical Center	Loveland	Colorado	United States	80539
29	Parker Adventist Hospital	Parker	Colorado	United States	80138
30	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
31	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
32	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
33	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
34	Beebe Medical Center	Lewes	Delaware	United States	19958
35	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
36	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
37	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
38	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
39	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
40	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
41	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware	United States	19973
42	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
43	AdventHealth Orlando	Orlando	Florida	United States	32803
44	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
45	Northwestern University	Chicago	Illinois	United States	60611
46	University of Illinois	Chicago	Illinois	United States	60612
47	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
48	Presence Saint Mary's Hospital	Kankakee	Illinois	United States	60901
49	AMG Libertyville - Oncology	Libertyville	Illinois	United States	60048
50	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
51	SwedishAmerican Regional Cancer Center/ACT	Rockford	Illinois	United States	61114
52	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
53	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
54	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
55	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
56	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
57	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
58	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
59	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
60	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
61	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
62	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
63	Cancer Center of Kansas-Manhattan	Manhattan	Kansas	United States	66502
64	Cancer Center of Kansas - McPherson	McPherson	Kansas	United States	67460
65	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
66	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
67	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
68	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
69	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
70	Associates In Womens Health	Wichita	Kansas	United States	67208
71	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
72	Ascension Via Christi Hospitals Wichita	Wichita	Kansas	United States	67214
73	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
74	Wesley Medical Center	Wichita	Kansas	United States	67214
75	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
76	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
77	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
78	Eastern Maine Medical Center	Bangor	Maine	United States	04401
79	Christiana Care - Union Hospital	Elkton	Maryland	United States	21921
80	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
81	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
82	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
83	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
84	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
85	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
86	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
87	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
88	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
89	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
90	Northwell Health NCORP	Lake Success	New York	United States	11042
91	Northwell Health/Center for Advanced Medicine	Lake Success	New York	United States	11042
92	North Shore University Hospital	Manhasset	New York	United States	11030
93	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
94	NYP/Weill Cornell Medical Center	New York	New York	United States	10065
95	University of Rochester	Rochester	New York	United States	14642
96	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
97	The Jewish Hospital	Cincinnati	Ohio	United States	45236
98	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
99	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
100	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
101	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Matthew J Wieduwilt, Alliance for Clinical Trials in Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 21, 2017

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01256398
• Other Study ID Numbers: NCI-2011-02621; NCI-2011-02621; CALGB 10701/CTSU C10701; CDR0000690286; CALGB-10701; CALGB-10701; U10CA180821; U10CA031946
• First Posted: Dec 8, 2010
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Melphalan; Mechlorethamine; Nitrogen Mustard Compounds; Methotrexate; Fludarabine; Fludarabine phosphate; Etoposide; Vincristine; Daunorubicin; Dasatinib; Mercaptopurine; Alemtuzumab; Etoposide phosphate; Antineoplastic Agents, Immunological; Tacrolimus; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; BB 1101; Calcium; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Treatment (Chemotherapy, Transplant)
Arm/Group Description	All enrolled patients.> > Alemtuzumab: Given IV> Allogeneic Hematopoietic Stem Cell Transplantation: Undergo peripheral blood allogeneic HCT> Autologous Hematopoietic Stem Cell Transplantation: Undergo peripheral blood autologous HCT> Cyclophosphamide: Given IV> Cytarabine: Given IV> Dasatinib: Given PO> Daunorubicin Hydrochloride: Given IV> Dexamethasone: Given PO or IV> Etoposide Phosphate: Given IV> Filgrastim: Given SC> Fludarabine Phosphate: Given IV> In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood autologous or allogeneic HCT> Laboratory Biomarker Analysis: Correlative studies> Leucovorin Calcium: Given IV or PO> Melphalan: Given IV> Mercaptopurine: Given PO> Methotrexate: Given IT, IV, or PO> Pegfilgrastim: Given SC> Pharmacological Study: Correlative studies> Tacrolimus: Given IV or PO> Vincristine Sulfate: Given IV
Period Title: Overall Study
STARTED	66
COMPLETED	65
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Chemotherapy, Transplant)
Arm/Group Description	All enrolled patients.> > Alemtuzumab: Given IV> Allogeneic Hematopoietic Stem Cell Transplantation: Undergo peripheral blood allogeneic HCT> Autologous Hematopoietic Stem Cell Transplantation: Undergo peripheral blood autologous HCT> Cyclophosphamide: Given IV> Cytarabine: Given IV> Dasatinib: Given PO> Daunorubicin Hydrochloride: Given IV> Dexamethasone: Given PO or IV> Etoposide Phosphate: Given IV> Filgrastim: Given SC> Fludarabine Phosphate: Given IV> In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood autologous or allogeneic HCT> Laboratory Biomarker Analysis: Correlative studies> Leucovorin Calcium: Given IV or PO> Melphalan: Given IV> Mercaptopurine: Given PO> Methotrexate: Given IT, IV, or PO> Pegfilgrastim: Given SC> Pharmacological Study: Correlative studies> Tacrolimus: Given IV or PO> Vincristine Sulfate: Given IV
Overall Participants	65
Age (Years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Years]	60.1
Sex: Female, Male (Count of Participants)
Female	33 50.8%
Male	32 49.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 15.4%
Not Hispanic or Latino	50 76.9%
Unknown or Not Reported	5 7.7%

Outcome Measures

1. Primary Outcome

Title	Disease Free Survival Defined From the Date of First Induction Complete Response (CR) to Relapse or Death Due to Any Cause
Description	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
Time Frame	At 3 years after CR

Outcome Measure Data

Analysis Population Description

All patients that reached CR and chose to continue with the study.

Arm/Group Title	Treatment (Chemotherapy, Transplant)
Arm/Group Description	All enrolled patients that reached CR during induction and continued to course 5.> > Alemtuzumab: Given IV> Allogeneic Hematopoietic Stem Cell Transplantation: Undergo peripheral blood allogeneic HCT> Autologous Hematopoietic Stem Cell Transplantation: Undergo peripheral blood autologous HCT> Cyclophosphamide: Given IV> Cytarabine: Given IV> Dasatinib: Given PO> Daunorubicin Hydrochloride: Given IV> Dexamethasone: Given PO or IV> Etoposide Phosphate: Given IV> Filgrastim: Given SC> Fludarabine Phosphate: Given IV> In Vitro-Treated Peripheral Blood Stem Cell Transplantation: Undergo peripheral blood autologous or allogeneic HCT> Laboratory Biomarker Analysis: Correlative studies> Leucovorin Calcium: Given IV or PO> Melphalan: Given IV> Mercaptopurine: Given PO> Methotrexate: Given IT, IV, or PO> Pegfilgrastim: Given SC> Pharmacological Study: Correlative studies> Tacrolimus: Given IV or PO> Vincristine Sulfate: Given IV
Measure Participants	38
Number (95% Confidence Interval) [percentage of patients]	52.6

2. Secondary Outcome

Title	Probability of Being BCR-ABL Negative in the Bone Marrow and Peripheral Blood at the Completion of the CNS Prophylaxis Course (Restricted to Those Patients Achieving a CR)
Description	Proportions will be estimated based on the combined and individual cohorts.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Feasibility of Maintenance Therapy in This Patient Population (Restricted to Those Patients Achieving a CR)
Description	Proportions will be estimated based on the combined and individual cohorts.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	OS
Description	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	DFS
Description	Estimated using the Kaplan-Meier estimator. Proportions will be estimated using point as well as interval estimators. All interval estimators will be constructed using the finite sample size sampling distribution at the unadjusted two-sided level of 0.05.
Time Frame	From the date of first induction CR to relapse, or death due to any cause, with patients last known to be alive and disease-free censored at the date of last contact, assessed up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Response
Time Frame	Up to 10 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 to determine the severity of the reaction for adverse event reporting.
Arm/Group Title	Treatment (Chemotherapy, Transplant)
Arm/Group Description	Vincristine Sulfate: Given IV
All Cause Mortality
	Treatment (Chemotherapy, Transplant)
	Affected / at Risk (%)	# Events
Total	5/65 (7.7%)
Serious Adverse Events
	Treatment (Chemotherapy, Transplant)
	Affected / at Risk (%)	# Events
Total	5/65 (7.7%)
General disorders
Multi-organ failure	1/65 (1.5%)	1
Infections and infestations
Lung infection	1/65 (1.5%)	1
Sepsis	1/65 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	1/65 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/65 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Chemotherapy, Transplant)
	Affected / at Risk (%)	# Events
Total	65/65 (100%)
Blood and lymphatic system disorders
Anemia	59/65 (90.8%)	535
Blood and lymphatic system disorders - Other, specify	4/65 (6.2%)	5
Disseminated intravascular coagulation	10/65 (15.4%)	18
Febrile neutropenia	27/65 (41.5%)	41
Hemolysis	1/65 (1.5%)	1
Leukocytosis	6/65 (9.2%)	6
Lymph node pain	1/65 (1.5%)	1
Thrombotic thrombocytopenic purpura	1/65 (1.5%)	1
Cardiac disorders
Atrial fibrillation	4/65 (6.2%)	4
Cardiac disorders - Other, specify	6/65 (9.2%)	9
Chest pain - cardiac	5/65 (7.7%)	5
Heart failure	2/65 (3.1%)	2
Left ventricular systolic dysfunction	1/65 (1.5%)	1
Mitral valve disease	1/65 (1.5%)	1
Myocardial infarction	4/65 (6.2%)	4
Palpitations	6/65 (9.2%)	12
Pericardial effusion	3/65 (4.6%)	6
Pericarditis	1/65 (1.5%)	1
Pulmonary valve disease	1/65 (1.5%)	1
Sinus bradycardia	3/65 (4.6%)	3
Sinus tachycardia	14/65 (21.5%)	35
Supraventricular tachycardia	3/65 (4.6%)	8
Tricuspid valve disease	1/65 (1.5%)	1
Ventricular arrhythmia	2/65 (3.1%)	3
Ventricular tachycardia	2/65 (3.1%)	2
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify	1/65 (1.5%)	1
Ear pain	2/65 (3.1%)	2
External ear pain	1/65 (1.5%)	1
Tinnitus	1/65 (1.5%)	1
Vertigo	2/65 (3.1%)	2
Vestibular disorder	1/65 (1.5%)	1
Endocrine disorders
Cushingoid	1/65 (1.5%)	1
Endocrine disorders - Other, specify	1/65 (1.5%)	1
Hyperthyroidism	1/65 (1.5%)	1
Hypothyroidism	4/65 (6.2%)	5
Eye disorders
Blurred vision	11/65 (16.9%)	16
Conjunctivitis	1/65 (1.5%)	1
Dry eye	7/65 (10.8%)	10
Extraocular muscle paresis	1/65 (1.5%)	1
Eye disorders - Other, specify	3/65 (4.6%)	3
Eye pain	2/65 (3.1%)	2
Eyelid function disorder	1/65 (1.5%)	1
Floaters	2/65 (3.1%)	2
Photophobia	2/65 (3.1%)	5
Watering eyes	2/65 (3.1%)	3
Gastrointestinal disorders
Abdominal distension	6/65 (9.2%)	9
Abdominal pain	26/65 (40%)	54
Anal fistula	1/65 (1.5%)	1
Anal hemorrhage	3/65 (4.6%)	3
Anal pain	2/65 (3.1%)	4
Ascites	2/65 (3.1%)	2
Bloating	5/65 (7.7%)	9
Colitis	6/65 (9.2%)	9
Colonic hemorrhage	1/65 (1.5%)	1
Colonic perforation	2/65 (3.1%)	2
Constipation	37/65 (56.9%)	71
Diarrhea	47/65 (72.3%)	182
Dry mouth	8/65 (12.3%)	16
Dyspepsia	13/65 (20%)	16
Dysphagia	8/65 (12.3%)	11
Esophageal pain	1/65 (1.5%)	1
Esophagitis	4/65 (6.2%)	6
Flatulence	3/65 (4.6%)	5
Gastric hemorrhage	2/65 (3.1%)	2
Gastric ulcer	1/65 (1.5%)	1
Gastritis	3/65 (4.6%)	3
Gastroesophageal reflux disease	13/65 (20%)	22
Gastrointestinal disorders - Other, specify	12/65 (18.5%)	19
Hemorrhoidal hemorrhage	3/65 (4.6%)	3
Hemorrhoids	3/65 (4.6%)	3
Ileus	1/65 (1.5%)	2
Lower gastrointestinal hemorrhage	2/65 (3.1%)	8
Mucositis oral	30/65 (46.2%)	39
Nausea	47/65 (72.3%)	199
Oral pain	2/65 (3.1%)	2
Rectal hemorrhage	1/65 (1.5%)	3
Rectal pain	3/65 (4.6%)	3
Small intestinal mucositis	1/65 (1.5%)	1
Stomach pain	5/65 (7.7%)	6
Toothache	1/65 (1.5%)	1
Upper gastrointestinal hemorrhage	1/65 (1.5%)	1
Vomiting	40/65 (61.5%)	106
General disorders
Chills	20/65 (30.8%)	31
Edema face	2/65 (3.1%)	2
Edema limbs	31/65 (47.7%)	98
Facial pain	1/65 (1.5%)	1
Fatigue	59/65 (90.8%)	318
Fever	28/65 (43.1%)	62
Gait disturbance	3/65 (4.6%)	6
General disorders and administration site conditions - Other, specify	7/65 (10.8%)	10
Infusion related reaction	4/65 (6.2%)	4
Injection site reaction	1/65 (1.5%)	1
Localized edema	4/65 (6.2%)	5
Malaise	6/65 (9.2%)	17
Multi-organ failure	2/65 (3.1%)	2
Neck edema	1/65 (1.5%)	1
Non-cardiac chest pain	11/65 (16.9%)	14
Pain	16/65 (24.6%)	42
Immune system disorders
Allergic reaction	2/65 (3.1%)	2
Infections and infestations
Appendicitis	1/65 (1.5%)	1
Bladder infection	1/65 (1.5%)	1
Bronchial infection	3/65 (4.6%)	3
Catheter related infection	7/65 (10.8%)	10
Enterocolitis infectious	6/65 (9.2%)	14
Hepatic infection	1/65 (1.5%)	1
Infections and infestations - Other, specify	18/65 (27.7%)	31
Infective myositis	1/65 (1.5%)	1
Joint infection	1/65 (1.5%)	5
Lip infection	1/65 (1.5%)	1
Lung infection	14/65 (21.5%)	33
Mucosal infection	6/65 (9.2%)	9
Otitis media	1/65 (1.5%)	1
Papulopustular rash	1/65 (1.5%)	2
Phlebitis infective	1/65 (1.5%)	1
Prostate infection	1/65 (1.5%)	1
Rash pustular	3/65 (4.6%)	3
Salivary gland infection	1/65 (1.5%)	1
Sepsis	5/65 (7.7%)	7
Sinusitis	11/65 (16.9%)	15
Skin infection	7/65 (10.8%)	18
Soft tissue infection	2/65 (3.1%)	2
Tooth infection	1/65 (1.5%)	1
Upper respiratory infection	18/65 (27.7%)	28
Urinary tract infection	14/65 (21.5%)	30
Vaginal infection	2/65 (3.1%)	2
Wound infection	1/65 (1.5%)	2
Injury, poisoning and procedural complications
Ankle fracture	1/65 (1.5%)	1
Bruising	13/65 (20%)	24
Fall	8/65 (12.3%)	11
Fracture	2/65 (3.1%)	2
Postoperative hemorrhage	3/65 (4.6%)	3
Wound dehiscence	1/65 (1.5%)	1
Investigations
Activated partial thromboplastin time prolonged	12/65 (18.5%)	16
Alanine aminotransferase increased	48/65 (73.8%)	204
Alkaline phosphatase increased	37/65 (56.9%)	149
Aspartate aminotransferase increased	45/65 (69.2%)	216
Blood bilirubin increased	23/65 (35.4%)	37
Cardiac troponin I increased	5/65 (7.7%)	6
Cholesterol high	1/65 (1.5%)	1
Creatinine increased	28/65 (43.1%)	116
Electrocardiogram QT corrected interval prolonged	8/65 (12.3%)	17
Fibrinogen decreased	10/65 (15.4%)	10
Haptoglobin decreased	2/65 (3.1%)	2
INR increased	16/65 (24.6%)	22
Investigations - Other, specify	8/65 (12.3%)	32
Lymphocyte count decreased	41/65 (63.1%)	212
Lymphocyte count increased	4/65 (6.2%)	4
Neutrophil count decreased	61/65 (93.8%)	342
Platelet count decreased	63/65 (96.9%)	413
Serum amylase increased	1/65 (1.5%)	1
Weight gain	5/65 (7.7%)	5
Weight loss	11/65 (16.9%)	121
White blood cell decreased	54/65 (83.1%)	284
Metabolism and nutrition disorders
Acidosis	4/65 (6.2%)	4
Alkalosis	1/65 (1.5%)	1
Anorexia	33/65 (50.8%)	98
Dehydration	10/65 (15.4%)	13
Hypercalcemia	6/65 (9.2%)	11
Hyperglycemia	51/65 (78.5%)	284
Hyperkalemia	17/65 (26.2%)	37
Hypermagnesemia	21/65 (32.3%)	32
Hypernatremia	15/65 (23.1%)	25
Hypertriglyceridemia	7/65 (10.8%)	16
Hyperuricemia	11/65 (16.9%)	53
Hypoalbuminemia	44/65 (67.7%)	189
Hypocalcemia	45/65 (69.2%)	129
Hypoglycemia	11/65 (16.9%)	27
Hypokalemia	46/65 (70.8%)	151
Hypomagnesemia	28/65 (43.1%)	80
Hyponatremia	38/65 (58.5%)	122
Hypophosphatemia	29/65 (44.6%)	61
Metabolism and nutrition disorders - Other, specify	3/65 (4.6%)	29
Tumor lysis syndrome	6/65 (9.2%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	21/65 (32.3%)	34
Arthritis	1/65 (1.5%)	2
Back pain	28/65 (43.1%)	51
Bone pain	7/65 (10.8%)	8
Buttock pain	1/65 (1.5%)	1
Chest wall pain	2/65 (3.1%)	3
Flank pain	1/65 (1.5%)	1
Generalized muscle weakness	14/65 (21.5%)	35
Joint effusion	1/65 (1.5%)	1
Joint range of motion decreased	1/65 (1.5%)	1
Muscle weakness lower limb	4/65 (6.2%)	6
Musculoskeletal and connective tissue disorder - Other, specify	4/65 (6.2%)	5
Myalgia	11/65 (16.9%)	15
Neck pain	9/65 (13.8%)	17
Pain in extremity	16/65 (24.6%)	38
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	2/65 (3.1%)	2
Nervous system disorders
Ataxia	1/65 (1.5%)	1
Depressed level of consciousness	1/65 (1.5%)	1
Dizziness	22/65 (33.8%)	43
Dysgeusia	8/65 (12.3%)	14
Dysphasia	1/65 (1.5%)	1
Facial muscle weakness	1/65 (1.5%)	1
Headache	32/65 (49.2%)	86
Hypersomnia	1/65 (1.5%)	2
Intracranial hemorrhage	1/65 (1.5%)	1
Lethargy	5/65 (7.7%)	6
Memory impairment	1/65 (1.5%)	1
Movements involuntary	1/65 (1.5%)	1
Nervous system disorders - Other, specify	4/65 (6.2%)	7
Neuralgia	1/65 (1.5%)	1
Paresthesia	1/65 (1.5%)	1
Peripheral motor neuropathy	7/65 (10.8%)	9
Peripheral sensory neuropathy	25/65 (38.5%)	118
Phantom pain	1/65 (1.5%)	1
Presyncope	1/65 (1.5%)	1
Reversible posterior leukoencephalopathy syndrome	1/65 (1.5%)	1
Sinus pain	1/65 (1.5%)	1
Somnolence	3/65 (4.6%)	5
Syncope	3/65 (4.6%)	3
Tremor	7/65 (10.8%)	7
Psychiatric disorders
Agitation	1/65 (1.5%)	1
Anxiety	20/65 (30.8%)	56
Confusion	6/65 (9.2%)	9
Delirium	1/65 (1.5%)	2
Delusions	1/65 (1.5%)	1
Depression	11/65 (16.9%)	34
Hallucinations	4/65 (6.2%)	6
Insomnia	28/65 (43.1%)	51
Libido decreased	1/65 (1.5%)	1
Libido increased	1/65 (1.5%)	1
Psychiatric disorders - Other, specify	2/65 (3.1%)	2
Restlessness	2/65 (3.1%)	2
Renal and urinary disorders
Acute kidney injury	13/65 (20%)	39
Bladder spasm	1/65 (1.5%)	3
Chronic kidney disease	8/65 (12.3%)	36
Cystitis noninfective	1/65 (1.5%)	1
Hematuria	6/65 (9.2%)	10
Proteinuria	13/65 (20%)	19
Renal and urinary disorders - Other, specify	8/65 (12.3%)	10
Urinary frequency	9/65 (13.8%)	11
Urinary incontinence	3/65 (4.6%)	6
Urinary retention	3/65 (4.6%)	4
Urinary tract pain	3/65 (4.6%)	7
Urinary urgency	3/65 (4.6%)	3
Reproductive system and breast disorders
Testicular pain	1/65 (1.5%)	1
Uterine pain	2/65 (3.1%)	2
Vaginal hemorrhage	3/65 (4.6%)	6
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	7/65 (10.8%)	13
Atelectasis	7/65 (10.8%)	7
Bronchopulmonary hemorrhage	2/65 (3.1%)	2
Cough	33/65 (50.8%)	72
Dyspnea	35/65 (53.8%)	118
Epistaxis	7/65 (10.8%)	7
Hiccups	4/65 (6.2%)	4
Hoarseness	2/65 (3.1%)	2
Hypoxia	7/65 (10.8%)	7
Laryngeal hemorrhage	1/65 (1.5%)	1
Nasal congestion	12/65 (18.5%)	20
Pharyngeal mucositis	1/65 (1.5%)	1
Pharyngolaryngeal pain	1/65 (1.5%)	1
Pleural effusion	26/65 (40%)	60
Pleuritic pain	1/65 (1.5%)	1
Pneumonitis	2/65 (3.1%)	2
Postnasal drip	4/65 (6.2%)	7
Productive cough	8/65 (12.3%)	12
Pulmonary edema	6/65 (9.2%)	6
Pulmonary hypertension	1/65 (1.5%)	1
Respiratory failure	2/65 (3.1%)	2
Respiratory, thoracic and mediastinal disorders - Other, specify	6/65 (9.2%)	10
Sleep apnea	1/65 (1.5%)	1
Sore throat	18/65 (27.7%)	23
Wheezing	7/65 (10.8%)	7
Skin and subcutaneous tissue disorders
Alopecia	7/65 (10.8%)	12
Bullous dermatitis	1/65 (1.5%)	1
Dry skin	14/65 (21.5%)	36
Erythema multiforme	3/65 (4.6%)	3
Nail loss	1/65 (1.5%)	1
Pain of skin	1/65 (1.5%)	1
Palmar-plantar erythrodysesthesia syndrome	1/65 (1.5%)	1
Periorbital edema	2/65 (3.1%)	6
Pruritus	19/65 (29.2%)	30
Purpura	6/65 (9.2%)	12
Rash acneiform	5/65 (7.7%)	12
Rash maculo-papular	34/65 (52.3%)	79
Scalp pain	1/65 (1.5%)	1
Skin and subcutaneous tissue disorders - Other, specify	16/65 (24.6%)	56
Skin induration	2/65 (3.1%)	6
Skin ulceration	3/65 (4.6%)	3
Urticaria	7/65 (10.8%)	11
Surgical and medical procedures
Surgical and medical procedures - Other, specify	1/65 (1.5%)	1
Vascular disorders
Flushing	5/65 (7.7%)	6
Hematoma	6/65 (9.2%)	8
Hot flashes	7/65 (10.8%)	15
Hypertension	21/65 (32.3%)	68
Hypotension	16/65 (24.6%)	27
Superficial thrombophlebitis	2/65 (3.1%)	2
Thromboembolic event	7/65 (10.8%)	13

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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