Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00039377
• Collaborator: (none)
• Enrollment: 58
• Locations: 97
• Arm: 1
• Duration (Months): 142.1
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Adult Acute Lymphoblastic Leukemia in Remission	Drug: imatinib mesylate; Drug: methotrexate; Drug: vincristine sulfate; Drug: leucovorin calcium; Procedure: peripheral blood stem cell transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Radiation: total-body irradiation; Drug: tacrolimus; Biological: filgrastim; Drug: etoposide; Drug: cyclophosphamide; Drug: cytarabine; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).

2. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.

3. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.

4. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).

5. Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).

6. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.

OUTLINE:

COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to enrollment.

COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.

COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.

COURSE IV (imatinib mesylate): After blood counts recover after completion of course III, patients receive imatinib mesylate as in course II.

COURSE V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT, or no PBSCT.

COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen [HLA]-matched sibling donor): Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive filgrastim SC beginning on day 0 and continuing until blood counts recover.

COURSE Vc (no transplantation for patients who are not transplant candidates): Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts recover.

COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation or on day 30 if no transplantation received and continuing for at least 1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain reaction assays at least 3 months apart or until relapse.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (imatinib mesylate, chemotherapy, PBSCT) See Detailed Description.

Drug: imatinib mesylate; Given PO; Other Names: CGP 57148 Gleevec Glivec ; Drug: methotrexate; Given IT and IV; Other Names: amethopterin Folex methylaminopterin Mexate MTX ; Drug: vincristine sulfate; Given IV; Other Names: leurocristine sulfate VCR Vincasar PFS ; Drug: leucovorin calcium; Given IV and PO; Other Names: CF CFR LV ; Procedure: peripheral blood stem cell transplantation; Undergo PBSCT; Other Names: PBPC transplantation PBSC transplantation peripheral blood progenitor cell transplantation transplantation, peripheral blood stem cell ; Procedure: autologous hematopoietic stem cell transplantation; Undergo autologous PBSCT; Procedure: allogeneic hematopoietic stem cell transplantation; Undergo allogeneic PBSCT; Radiation: total-body irradiation; Undergo TBI; Other Names: TBI ; Drug: tacrolimus; Given IV or PO; Other Names: FK 506 Prograf ; Biological: filgrastim; Given SC; Other Names: G-CSF Neupogen ; Drug: etoposide; Given IV; Other Names: EPEG VP-16 VP-16-213 ; Drug: cyclophosphamide; Given IV; Other Names: CPM CTX Cytoxan Endoxan Endoxana ; Drug: cytarabine; Given IV; Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside ; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Disease Free Survival [Duration of treatment (up to 10 years)]

   Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method. A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.

Secondary Outcome Measures

1. Overall Survival [Duration of study (up to 10 years)]

   Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.

2. Number of Participants Who Achieved a BCR-ABL Response at 12 Months [12 months]

   BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR). Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).

3. 5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups [5 years from CR]

   Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.

4. 5 Year Overall Survival for Autologous & Allogeneic Transplant Groups [5 years from registration]

   Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 59 Years
• 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 by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})

• Prior Therapy:

• Complete or partial remission following one course of induction chemotherapy with an intensive 4 or 5 drug regimen (with or without imatinib mesylate) on a CALGB or SWOG ALL protocol for previously untreated ALL patients

• Note: The double induction regimen of SWOG S0333 is considered to be one course of induction chemotherapy for the purpose of this eligibility criterion; therefore, patients from S0333 may be eligible for this study only after completing the entire double induction regimen

• Complete or partial remission following one course of therapy on any standard induction regimen (with or without imatinib mesylate) without prior enrollment on a cooperative group frontline protocol; in these instances, documentation of Philadelphia chromosome (Ph)+ positivity may occur outside a CALGB or SWOG laboratory

• Note: CALGB institutions must enroll patients on CALGB 9862 and submission of an initial sample for the companion trial must occur at time of enrollment on CALGB C10001; enrollment on companion studies CALGB 8461 and 9665 is not required

• No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment

• 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 imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342
2	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
3	Graham Hospital Association	Canton	Illinois	United States	61520
4	Memorial Hospital	Carthage	Illinois	United States	62321
5	University of Chicago	Chicago	Illinois	United States	60637
6	Weiss Memorial Hospital	Chicago	Illinois	United States	60640
7	Eureka Hospital	Eureka	Illinois	United States	61530
8	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
9	Illinois CancerCare Galesburg	Galesburg	Illinois	United States	61401
10	Mason District Hospital	Havana	Illinois	United States	62644
11	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
12	Mcdonough District Hospital	Macomb	Illinois	United States	61455
13	Loyola University Medical Center	Maywood	Illinois	United States	60153
14	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
15	Community Cancer Center Foundation	Normal	Illinois	United States	61761
16	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
17	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
18	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
19	Pekin Hospital	Pekin	Illinois	United States	61554
20	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
21	Proctor Hospital	Peoria	Illinois	United States	61614
22	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
23	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
24	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
25	Illinois Valley Hospital	Peru	Illinois	United States	61354
26	Perry Memorial Hospital	Princeton	Illinois	United States	61356
27	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
28	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
29	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
30	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
31	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
32	Providence Medical Center	Kansas City	Kansas	United States	66112
33	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
34	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
35	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
36	Radiation Oncology Center of Olathe	Olathe	Kansas	United States	66061
37	Radiation Oncology Practice Corporation Southwest	Overland Park	Kansas	United States	66210
38	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
39	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
40	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
41	Salina Regional Health Center	Salina	Kansas	United States	67401
42	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
43	Associates In Womens Health	Wichita	Kansas	United States	67208
44	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
45	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
46	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
47	Wichita CCOP	Wichita	Kansas	United States	67214
48	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
49	Eastern Maine Medical Center	Bangor	Maine	United States	04401
50	Beverly Hospital	Beverly	Massachusetts	United States	01915
51	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
52	Commonwealth Hematology Oncology PC-Worcester	Worcester	Massachusetts	United States	01605
53	Centerpoint Medical Center LLC	Independence	Missouri	United States	64057
54	Saint Luke's Cancer Institute	Kansas City	Missouri	United States	64111
55	Radiation Oncology Practice Corporation South	Kansas City	Missouri	United States	64114
56	Radiation Oncology Practice Corporation - North	Kansas City	Missouri	United States	64154
57	Liberty Hospital	Liberty	Missouri	United States	64068
58	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
59	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
60	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
61	Saint Vincent Healthcare	Billings	Montana	United States	59101
62	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59102
63	Billings Clinic	Billings	Montana	United States	59107-7000
64	Deaconess Medical Center	Billings	Montana	United States	59107
65	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
66	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
67	Internal Medicine of Bozeman	Bozeman	Montana	United States	59715
68	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
69	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
70	Great Falls Clinic	Great Falls	Montana	United States	59405
71	Saint Peter's Community Hospital	Helena	Montana	United States	59601
72	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
73	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
74	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
75	Community Medical Hospital	Missoula	Montana	United States	59801
76	Montana Cancer Specialists	Missoula	Montana	United States	59802
77	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
78	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
79	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire	United States	03431
80	Frisbie Hospital	Rochester	New Hampshire	United States	03867
81	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
82	North Shore University Hospital	Manhasset	New York	United States	11030
83	North Shore-LIJ Health System CCOP	Manhasset	New York	United States	11030
84	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
85	North Shore-LIJ Health System/Center for Advanced Medicine	New Hyde Park	New York	United States	11040
86	Weill Medical College of Cornell University	New York	New York	United States	10065
87	Oswego Hospital	Oswego	New York	United States	13126
88	University of Rochester	Rochester	New York	United States	14642
89	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
90	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
91	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
92	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210
93	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224-1791
94	Medical University of South Carolina	Charleston	South Carolina	United States	29425
95	Northeastern	St. Johnsbury	Vermont	United States	05819
96	Virginia Commonwealth University	Richmond	Virginia	United States	23298
97	Welch Cancer Center	Sheridan	Wyoming	United States	82801

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Meir Wetzler, Cancer and Leukemia Group B

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00039377
• Other Study ID Numbers: NCI-2009-00436; NCI-2009-00436; CDR0000069378; CALGB 10001/SWOG C10001; CALGB-10001; U10CA031946; NCT01648426
• First Posted: Jan 27, 2003
• Last Update Posted: Nov 24, 2014
• Last Verified: Jun 1, 2014

• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leucovorin; Cytarabine; Cyclophosphamide; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Imatinib Mesylate; Tacrolimus; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	58 participants were recruited.
Pre-assignment Detail	One participant was deemed ineligible and is excluded from all analyses per study design.

Arm/Group Title	Entire Cohort	Patients With HLA-matched Sibling Donor in Course 5	Patients Without HLA-matched Sibling Donors in Course V	Patients Who Did Not Undergo Transplant for Course V
Arm/Group Description	All participants treatment on this study, see the Detailed Description for treatment information.	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Period Title: Initial Registration
STARTED	57	0	0	0
COMPLETED	35	0	0	0
NOT COMPLETED	22	0	0	0
Period Title: Initial Registration
STARTED	0	15	19	1
COMPLETED	0	15	19	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Cohort
Arm/Group Description	All participants treatment on this study, see the Detailed Description for treatment information.
Overall Participants	57
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	44
Sex: Female, Male (Count of Participants)
Female	32 56.1%
Male	25 43.9%
Region of Enrollment (participants) [Number]
United States	57 100%

Outcome Measures

1. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
Time Frame	Duration of study (up to 10 years)

Outcome Measure Data

Analysis Population Description

OS Analysis was powered to include all participants.

Arm/Group Title	Entire Cohort
Arm/Group Description	All participants treatment on this study, see the Detailed Description for treatment information.
Measure Participants	57
Median (95% Confidence Interval) [years]	3.6

2. Secondary Outcome

Title	Number of Participants Who Achieved a BCR-ABL Response at 12 Months
Description	BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR). Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Peripheral blood stem cells were assayed from 13 patients.

Arm/Group Title	Entire Cohort
Arm/Group Description	All participants treatment on this study, see the Detailed Description for treatment information.
Measure Participants	13
Complete Molecular Response	9 15.8%
Major Molecular Response	4 7%

3. Primary Outcome

Title	Disease Free Survival
Description	Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method. A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.
Time Frame	Duration of treatment (up to 10 years)

Outcome Measure Data

Analysis Population Description

One participant was excluded per study design as they did not achieve a complete remission. DFS Analysis was powered to include all patients.

Arm/Group Title	Entire Cohort
Arm/Group Description	All participants treatment on this study, see the Detailed Description for treatment information.
Measure Participants	56
Median (95% Confidence Interval) [years]	1.7

4. Secondary Outcome

Title	5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups
Description	Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Time Frame	5 years from CR

Outcome Measure Data

Analysis Population Description

Participants who received autologous or allogeneic transplants were analyzed (N=34)

Arm/Group Title	Patients With HLA-matched Sibling Donor	Patients Without HLA-matched Sibling Donors
Arm/Group Description	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Measure Participants	15	19
Number (95% Confidence Interval) [percentage of patients]	46	47

5. Secondary Outcome

Title	5 Year Overall Survival for Autologous & Allogeneic Transplant Groups
Description	Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Time Frame	5 years from registration

Outcome Measure Data

Analysis Population Description

Participants who were on autologous or allogeneic transplant arms were analyzed (N=34).

Arm/Group Title	Patients With HLA-matched Sibling Donor	Patients Without HLA-matched Sibling Donors
Arm/Group Description	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
Measure Participants	15	19
Number (95% Confidence Interval) [percentage of patients]	53	51

Adverse Events

Arm/Group Title	Patients With HLA-matched Sibling Donor		Patients Without HLA-matched Sibling Donors		Patients Who Did Not Undergo Transplant
Arm/Group Description	Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then PO or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.		Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT. Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.		Patients undergo courses I-IV as in Detailed Description. Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover. Patients then undergo course VI as in Detailed Description.
All Cause Mortality
	Patients With HLA-matched Sibling Donor		Patients Without HLA-matched Sibling Donors		Patients Who Did Not Undergo Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Patients With HLA-matched Sibling Donor		Patients Without HLA-matched Sibling Donors		Patients Who Did Not Undergo Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/15 (40%)		9/19 (47.4%)		3/23 (13%)
Blood and lymphatic system disorders
Febrile neutropenia	1/15 (6.7%)	1	2/19 (10.5%)	3	0/23 (0%)	0
Hemoglobin decreased	4/15 (26.7%)	8	8/19 (42.1%)	10	3/23 (13%)	5
Cardiac disorders
Arrhythmia	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Arrhythmia supraventricular	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Atrial fibrillation	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Cardiac disorder	1/15 (6.7%)	1	0/19 (0%)	0	2/23 (8.7%)	2
Edema	2/15 (13.3%)	3	2/19 (10.5%)	2	0/23 (0%)	0
Left ventricular failure	1/15 (6.7%)	2	0/19 (0%)	0	1/23 (4.3%)	1
Palpitations	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Pericardial effusion	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Sinus tachycardia	2/15 (13.3%)	2	2/19 (10.5%)	2	0/23 (0%)	0
Ventricular arrhythmia	2/15 (13.3%)	2	0/19 (0%)	0	1/23 (4.3%)	1
Eye disorders
Conjunctivitis	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Diplopia	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Dry eye syndrome	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Eye disorder	2/15 (13.3%)	3	0/19 (0%)	0	0/23 (0%)	0
Vision blurred	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Anal hemorrhage	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Constipation	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Diarrhea	3/15 (20%)	3	5/19 (26.3%)	5	2/23 (8.7%)	2
Dry mouth	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Esophagitis	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Gastritis	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Gastrointestinal disorder	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Gingival pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Mucositis due to radiation	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Mucositis oral	2/15 (13.3%)	3	4/19 (21.1%)	5	0/23 (0%)	0
Nausea	5/15 (33.3%)	8	7/19 (36.8%)	8	3/23 (13%)	4
Typhlitis	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Vomiting	3/15 (20%)	3	6/19 (31.6%)	6	1/23 (4.3%)	1
General disorders
Chest pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Chills	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Edema limbs	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Fatigue	4/15 (26.7%)	5	7/19 (36.8%)	7	2/23 (8.7%)	2
Fever	1/15 (6.7%)	1	0/19 (0%)	0	2/23 (8.7%)	2
Pain	1/15 (6.7%)	1	4/19 (21.1%)	4	2/23 (8.7%)	2
Infections and infestations
Infection	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Infection with grade 3 or 4 neutropenia	2/15 (13.3%)	2	5/19 (26.3%)	5	0/23 (0%)	0
Infection without neutropenia	2/15 (13.3%)	2	3/19 (15.8%)	3	3/23 (13%)	3
Sepsis	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Alanine aminotransferase increased	4/15 (26.7%)	6	7/19 (36.8%)	7	1/23 (4.3%)	2
Alkaline phosphatase	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Alkaline phosphatase increased	1/15 (6.7%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Aspartate aminotransferase increased	4/15 (26.7%)	6	5/19 (26.3%)	5	1/23 (4.3%)	2
Blood bilirubin increased	2/15 (13.3%)	2	3/19 (15.8%)	3	0/23 (0%)	0
Creatinine increased	3/15 (20%)	5	2/19 (10.5%)	3	0/23 (0%)	0
Electrocardiogram QTc interval prolonged	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
INR increased	2/15 (13.3%)	3	1/19 (5.3%)	1	0/23 (0%)	0
Leukocyte count decreased	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Lymphocyte count decreased	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Neutrophil count decreased	4/15 (26.7%)	5	7/19 (36.8%)	8	2/23 (8.7%)	3
Platelet count decreased	5/15 (33.3%)	9	8/19 (42.1%)	10	1/23 (4.3%)	2
Weight loss	2/15 (13.3%)	3	0/19 (0%)	0	0/23 (0%)	0
Metabolism and nutrition disorders
Acidosis	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Alkalosis	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Anorexia	2/15 (13.3%)	3	2/19 (10.5%)	2	1/23 (4.3%)	1
Blood glucose increased	5/15 (33.3%)	8	4/19 (21.1%)	4	2/23 (8.7%)	4
Blood uric acid increased	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Dehydration	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Serum albumin decreased	2/15 (13.3%)	3	2/19 (10.5%)	2	1/23 (4.3%)	1
Serum calcium decreased	4/15 (26.7%)	6	3/19 (15.8%)	3	2/23 (8.7%)	2
Serum calcium increased	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Serum glucose decreased	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Serum magnesium decreased	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Serum magnesium increased	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Serum phosphate decreased	2/15 (13.3%)	3	2/19 (10.5%)	2	0/23 (0%)	0
Serum potassium decreased	3/15 (20%)	4	3/19 (15.8%)	4	2/23 (8.7%)	3
Serum potassium increased	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Serum sodium decreased	2/15 (13.3%)	3	2/19 (10.5%)	2	1/23 (4.3%)	1
Serum sodium increased	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Tumor lysis syndrome	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Musculoskeletal and connective tissue disorders
Buttock pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Muscle weakness	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Myalgia	0/15 (0%)	0	3/19 (15.8%)	3	1/23 (4.3%)	1
Pain in extremity	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Nervous system disorders
Ataxia	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Depressed level of consciousness	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Dizziness	1/15 (6.7%)	1	2/19 (10.5%)	2	1/23 (4.3%)	1
Headache	2/15 (13.3%)	2	0/19 (0%)	0	1/23 (4.3%)	1
Memory impairment	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Peripheral motor neuropathy	0/15 (0%)	0	1/19 (5.3%)	1	2/23 (8.7%)	2
Peripheral sensory neuropathy	2/15 (13.3%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Seizure	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Syncope	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Tremor	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Psychiatric disorders
Anxiety	1/15 (6.7%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Confusion	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Depression	2/15 (13.3%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Insomnia	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Renal and urinary disorders
Dysuria (painful urination)	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hematuria (in the absence of vaginal bleeding)	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Urinary retention	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Urogenital disorder	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Reproductive system and breast disorders
Vaginal hemorrhage	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	2/15 (13.3%)	3	0/19 (0%)	0	0/23 (0%)	0
Allergic rhinitis	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Cough	3/15 (20%)	4	1/19 (5.3%)	1	2/23 (8.7%)	2
Dyspnea	3/15 (20%)	3	1/19 (5.3%)	1	0/23 (0%)	0
Dyspnea (shortness of breath)	4/15 (26.7%)	5	1/19 (5.3%)	1	3/23 (13%)	3
Epistaxis	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hiccups	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hypoxia	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Pleural effusion	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Pneumonitis	2/15 (13.3%)	3	1/19 (5.3%)	1	0/23 (0%)	0
Pneumothorax	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Respiratory disorder	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Dry skin	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Pain of skin	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Pruritus	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Rash desquamating	4/15 (26.7%)	4	1/19 (5.3%)	1	0/23 (0%)	0
Skin disorder	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Vascular disorders
Flushing	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hot flashes	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hypotension	3/15 (20%)	3	4/19 (21.1%)	4	1/23 (4.3%)	1
Thrombosis	1/15 (6.7%)	1	3/19 (15.8%)	3	0/23 (0%)	0
Other (Not Including Serious) Adverse Events
	Patients With HLA-matched Sibling Donor		Patients Without HLA-matched Sibling Donors		Patients Who Did Not Undergo Transplant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		19/19 (100%)		21/23 (91.3%)
Blood and lymphatic system disorders
Blood disorder	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Febrile neutropenia	4/15 (26.7%)	4	10/19 (52.6%)	10	1/23 (4.3%)	1
Hemoglobin decreased	14/15 (93.3%)	70	19/19 (100%)	149	19/23 (82.6%)	53
Lymphatic disorder	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Transfusion: Platelets	1/15 (6.7%)	1	2/19 (10.5%)	2	0/23 (0%)	0
Transfusion: pRBCs	1/15 (6.7%)	2	2/19 (10.5%)	3	0/23 (0%)	0
Cardiac disorders
Arrhythmia	1/15 (6.7%)	1	2/19 (10.5%)	3	0/23 (0%)	0
Arrhythmia supraventricular	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Atrial fibrillation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Cardiac disorder	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	4
Cardiac pain	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Edema	9/15 (60%)	24	10/19 (52.6%)	25	9/23 (39.1%)	13
Left ventricular failure	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Myocardial ischemia	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Nodal arrhythmia	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Palpitations	3/15 (20%)	4	3/19 (15.8%)	3	1/23 (4.3%)	1
Sinus arrhythmia	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Sinus tachycardia	4/15 (26.7%)	4	4/19 (21.1%)	11	0/23 (0%)	0
Ventricular arrhythmia	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Ear and labyrinth disorders
Ear disorder	1/15 (6.7%)	3	1/19 (5.3%)	1	0/23 (0%)	0
Ear pain	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Hearing impaired	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Middle ear inflammation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Tinnitus	0/15 (0%)	0	1/19 (5.3%)	2	0/23 (0%)	0
Vertigo	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Endocrine disorders
Cushingoid	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Eye disorders
Dry eye syndrome	3/15 (20%)	19	2/19 (10.5%)	2	0/23 (0%)	0
Eye disorder	3/15 (20%)	3	2/19 (10.5%)	2	1/23 (4.3%)	1
Flashing vision	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Photophobia	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Vision blurred	2/15 (13.3%)	3	1/19 (5.3%)	1	1/23 (4.3%)	1
Watering eyes	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Gastrointestinal disorders
Abdominal distension	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Abdominal pain	3/15 (20%)	4	6/19 (31.6%)	12	2/23 (8.7%)	2
Colitis	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Constipation	2/15 (13.3%)	3	10/19 (52.6%)	14	2/23 (8.7%)	2
Diarrhea	12/15 (80%)	30	13/19 (68.4%)	42	9/23 (39.1%)	15
Dry mouth	5/15 (33.3%)	13	0/19 (0%)	0	0/23 (0%)	0
Dyspepsia	4/15 (26.7%)	9	3/19 (15.8%)	3	1/23 (4.3%)	1
Dysphagia	1/15 (6.7%)	1	4/19 (21.1%)	4	0/23 (0%)	0
Esophagitis	2/15 (13.3%)	2	4/19 (21.1%)	4	1/23 (4.3%)	1
Gastritis	0/15 (0%)	0	4/19 (21.1%)	6	2/23 (8.7%)	3
Gastrointestinal disorder	4/15 (26.7%)	7	3/19 (15.8%)	3	0/23 (0%)	0
Hemorrhoids	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Lower gastrointestinal hemorrhage	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Mucositis due to radiation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Mucositis oral	14/15 (93.3%)	19	13/19 (68.4%)	16	2/23 (8.7%)	2
Nausea	13/15 (86.7%)	39	18/19 (94.7%)	80	14/23 (60.9%)	28
Proctitis	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Rectal pain	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Stomatitis/pharyngitis (oral/pharyngeal mucositis) for BMT studies, if specified in	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Tooth disorder	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Vomiting	12/15 (80%)	23	15/19 (78.9%)	48	11/23 (47.8%)	17
General disorders
Chest pain	0/15 (0%)	0	3/19 (15.8%)	5	1/23 (4.3%)	1
Chills	2/15 (13.3%)	5	6/19 (31.6%)	8	2/23 (8.7%)	2
Edema limbs	0/15 (0%)	0	4/19 (21.1%)	7	1/23 (4.3%)	2
Fatigue	11/15 (73.3%)	43	17/19 (89.5%)	77	12/23 (52.2%)	26
Fever	5/15 (33.3%)	5	6/19 (31.6%)	12	5/23 (21.7%)	6
Ill-defined disorder	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Localized edema	0/15 (0%)	0	1/19 (5.3%)	4	0/23 (0%)	0
Pain	4/15 (26.7%)	7	7/19 (36.8%)	19	5/23 (21.7%)	5
Infections and infestations
Bladder infection	0/15 (0%)	0	1/19 (5.3%)	2	0/23 (0%)	0
Catheter related infection	0/15 (0%)	0	3/19 (15.8%)	3	0/23 (0%)	0
Colitis, infectious (e.g., Clostridium difficile)	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Gingival infection	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Infection	2/15 (13.3%)	2	4/19 (21.1%)	5	3/23 (13%)	4
Infection with grade 3 or 4 neutropenia	6/15 (40%)	8	8/19 (42.1%)	11	1/23 (4.3%)	1
Infection without neutropenia	6/15 (40%)	10	11/19 (57.9%)	19	4/23 (17.4%)	5
Pharyngitis	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Pneumonia	1/15 (6.7%)	1	1/19 (5.3%)	2	0/23 (0%)	0
Sinusitis	0/15 (0%)	0	1/19 (5.3%)	2	0/23 (0%)	0
Upper respiratory infection	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Wound-infectious	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Injury, poisoning and procedural complications
Bruising	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Dermatitis radiation	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Postoperative hemorrhage	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Radiation recall reaction (dermatologic)	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Wound dehiscence	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Investigations
Activated partial thromboplastin time prolonged	4/15 (26.7%)	4	8/19 (42.1%)	13	0/23 (0%)	0
Alanine aminotransferase increased	10/15 (66.7%)	26	12/19 (63.2%)	36	7/23 (30.4%)	11
Alkaline phosphatase	4/15 (26.7%)	6	4/19 (21.1%)	6	2/23 (8.7%)	3
Alkaline phosphatase increased	1/15 (6.7%)	1	4/19 (21.1%)	4	4/23 (17.4%)	6
Amylase increased	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Aspartate aminotransferase increased	11/15 (73.3%)	22	15/19 (78.9%)	44	9/23 (39.1%)	12
Blood bilirubin increased	6/15 (40%)	11	8/19 (42.1%)	11	2/23 (8.7%)	2
Coagulopathy	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Creatine phosphokinase increased	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	2
Creatinine increased	7/15 (46.7%)	14	8/19 (42.1%)	35	4/23 (17.4%)	5
Electrocardiogram QTc interval prolonged	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Gamma-glutamyltransferase increased	1/15 (6.7%)	4	0/19 (0%)	0	0/23 (0%)	0
INR increased	3/15 (20%)	3	3/19 (15.8%)	5	1/23 (4.3%)	2
Laboratory test abnormal	1/15 (6.7%)	1	0/19 (0%)	0	2/23 (8.7%)	2
Leukocyte count decreased	7/15 (46.7%)	26	4/19 (21.1%)	28	9/23 (39.1%)	14
Leukocytes (total WBC) for BMT studies, if specified in the protocol.	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Lymphocyte count decreased	3/15 (20%)	8	3/19 (15.8%)	16	8/23 (34.8%)	14
Neutrophil count decreased	13/15 (86.7%)	42	17/19 (89.5%)	72	7/23 (30.4%)	20
Platelet count decreased	12/15 (80%)	43	19/19 (100%)	97	9/23 (39.1%)	14
Weight gain	5/15 (33.3%)	5	1/19 (5.3%)	3	1/23 (4.3%)	1
Weight loss	3/15 (20%)	3	2/19 (10.5%)	2	1/23 (4.3%)	1
Metabolism and nutrition disorders
Acidosis	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Anorexia	9/15 (60%)	15	13/19 (68.4%)	27	5/23 (21.7%)	5
Blood glucose increased	9/15 (60%)	40	16/19 (84.2%)	62	12/23 (52.2%)	22
Blood uric acid increased	0/15 (0%)	0	3/19 (15.8%)	3	0/23 (0%)	0
Dehydration	1/15 (6.7%)	1	2/19 (10.5%)	3	0/23 (0%)	0
Serum albumin decreased	5/15 (33.3%)	9	8/19 (42.1%)	20	5/23 (21.7%)	8
Serum calcium decreased	8/15 (53.3%)	20	10/19 (52.6%)	23	9/23 (39.1%)	12
Serum glucose decreased	2/15 (13.3%)	2	6/19 (31.6%)	9	0/23 (0%)	0
Serum magnesium decreased	8/15 (53.3%)	16	8/19 (42.1%)	16	1/23 (4.3%)	1
Serum magnesium increased	1/15 (6.7%)	1	3/19 (15.8%)	3	0/23 (0%)	0
Serum phosphate decreased	4/15 (26.7%)	9	6/19 (31.6%)	9	3/23 (13%)	3
Serum potassium decreased	8/15 (53.3%)	17	14/19 (73.7%)	49	9/23 (39.1%)	14
Serum potassium increased	1/15 (6.7%)	2	3/19 (15.8%)	4	0/23 (0%)	0
Serum sodium decreased	4/15 (26.7%)	11	5/19 (26.3%)	10	4/23 (17.4%)	5
Serum sodium increased	1/15 (6.7%)	2	1/19 (5.3%)	2	2/23 (8.7%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	4/15 (26.7%)	7	6/19 (31.6%)	9	3/23 (13%)	6
Arthritis	0/15 (0%)	0	0/19 (0%)	0	1/23 (4.3%)	1
Back pain	2/15 (13.3%)	5	0/19 (0%)	0	3/23 (13%)	3
Bone pain	2/15 (13.3%)	2	2/19 (10.5%)	2	2/23 (8.7%)	2
Buttock pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Chest wall pain	0/15 (0%)	0	2/19 (10.5%)	2	1/23 (4.3%)	1
Joint disorder	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Muscle weakness	3/15 (20%)	6	3/19 (15.8%)	3	1/23 (4.3%)	1
Musculoskeletal disorder	1/15 (6.7%)	1	1/19 (5.3%)	1	1/23 (4.3%)	1
Myalgia	8/15 (53.3%)	13	10/19 (52.6%)	23	5/23 (21.7%)	9
Myositis	1/15 (6.7%)	3	0/19 (0%)	0	0/23 (0%)	0
Neck pain	1/15 (6.7%)	2	0/19 (0%)	0	0/23 (0%)	0
Pain in extremity	0/15 (0%)	0	3/19 (15.8%)	5	0/23 (0%)	0
Nervous system disorders
Arachnoiditis	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Ataxia	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Depressed level of consciousness	0/15 (0%)	0	2/19 (10.5%)	3	0/23 (0%)	0
Dizziness	5/15 (33.3%)	10	9/19 (47.4%)	14	2/23 (8.7%)	2
Dysgeusia	3/15 (20%)	7	1/19 (5.3%)	1	1/23 (4.3%)	1
Extrapyramidal disorder	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Headache	12/15 (80%)	28	17/19 (89.5%)	40	12/23 (52.2%)	14
Memory impairment	1/15 (6.7%)	1	1/19 (5.3%)	1	2/23 (8.7%)	2
Neurological disorder NOS	1/15 (6.7%)	1	2/19 (10.5%)	2	0/23 (0%)	0
Nystagmus	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Peripheral motor neuropathy	4/15 (26.7%)	4	5/19 (26.3%)	12	1/23 (4.3%)	1
Peripheral sensory neuropathy	9/15 (60%)	20	14/19 (73.7%)	48	10/23 (43.5%)	17
Syncope	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Tremor	8/15 (53.3%)	15	2/19 (10.5%)	3	0/23 (0%)	0
Psychiatric disorders
Agitation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Anxiety	3/15 (20%)	7	7/19 (36.8%)	11	3/23 (13%)	3
Confusion	5/15 (33.3%)	5	4/19 (21.1%)	4	2/23 (8.7%)	2
Depression	3/15 (20%)	6	7/19 (36.8%)	11	3/23 (13%)	4
Insomnia	4/15 (26.7%)	4	7/19 (36.8%)	10	3/23 (13%)	4
Renal and urinary disorders
Dysuria (painful urination)	2/15 (13.3%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Hematuria (in the absence of vaginal bleeding)	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hemorrhage urinary tract	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Urinary frequency	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Urinary retention	0/15 (0%)	0	2/19 (10.5%)	2	0/23 (0%)	0
Urine discoloration	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Urogenital disorder	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Gynecomastia	0/15 (0%)	0	1/19 (5.3%)	2	0/23 (0%)	0
Irregular menstruation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Reproductive tract disorder	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Testicular pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Vaginal hemorrhage	1/15 (6.7%)	1	3/19 (15.8%)	3	0/23 (0%)	0
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	3/15 (20%)	3	2/19 (10.5%)	10	3/23 (13%)	4
Bronchospasm	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Cough	7/15 (46.7%)	16	12/19 (63.2%)	23	2/23 (8.7%)	2
Dyspnea	3/15 (20%)	4	1/19 (5.3%)	3	0/23 (0%)	0
Dyspnea (shortness of breath)	5/15 (33.3%)	6	9/19 (47.4%)	12	1/23 (4.3%)	1
Epistaxis	1/15 (6.7%)	1	6/19 (31.6%)	6	0/23 (0%)	0
Hypoxia	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Pharyngolaryngeal pain	0/15 (0%)	0	1/19 (5.3%)	1	1/23 (4.3%)	1
Pleural effusion	1/15 (6.7%)	2	0/19 (0%)	0	2/23 (8.7%)	2
Pleuritic pain	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Pneumonitis	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Respiratory disorder	0/15 (0%)	0	4/19 (21.1%)	4	0/23 (0%)	0
Voice alteration	1/15 (6.7%)	1	1/19 (5.3%)	1	0/23 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	6/15 (40%)	10	5/19 (26.3%)	9	3/23 (13%)	6
Dry skin	2/15 (13.3%)	4	3/19 (15.8%)	3	1/23 (4.3%)	1
Erythema multiforme	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Hand-and-foot syndrome	2/15 (13.3%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Nail disorder	1/15 (6.7%)	1	0/19 (0%)	0	1/23 (4.3%)	1
Petechiae	2/15 (13.3%)	2	3/19 (15.8%)	3	0/23 (0%)	0
Photosensitivity	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Pigmentation changes (e.g., vitiligo)	1/15 (6.7%)	2	2/19 (10.5%)	2	1/23 (4.3%)	2
Pruritus	2/15 (13.3%)	3	3/19 (15.8%)	4	0/23 (0%)	0
Rash acneiform	1/15 (6.7%)	3	0/19 (0%)	0	0/23 (0%)	0
Rash desquamating	11/15 (73.3%)	20	11/19 (57.9%)	16	5/23 (21.7%)	6
Rash/dermatitis associated with high-dose chemotherapy or BMT studies.	1/15 (6.7%)	1	0/19 (0%)	0	0/23 (0%)	0
Rash/desquamation associated with graft versus host disease (GVHD) for BMT studies	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Skin disorder	4/15 (26.7%)	4	3/19 (15.8%)	3	0/23 (0%)	0
Skin hyperpigmentation	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Skin hypopigmentation	0/15 (0%)	0	1/19 (5.3%)	3	0/23 (0%)	0
Sweating	0/15 (0%)	0	1/19 (5.3%)	1	2/23 (8.7%)	2
Vascular disorders
Flushing	2/15 (13.3%)	2	1/19 (5.3%)	1	0/23 (0%)	0
Hemorrhage	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	2/15 (13.3%)	2	2/19 (10.5%)	2	0/23 (0%)	0
Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia	2/15 (13.3%)	2	0/19 (0%)	0	0/23 (0%)	0
Hot flashes	0/15 (0%)	0	1/19 (5.3%)	1	0/23 (0%)	0
Hypertension	4/15 (26.7%)	5	4/19 (21.1%)	6	2/23 (8.7%)	2
Hypotension	2/15 (13.3%)	2	3/19 (15.8%)	6	2/23 (8.7%)	2
Thrombosis	1/15 (6.7%)	1	3/19 (15.8%)	5	0/23 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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