CINJALL: Treatment for Children With Acute Lymphocytic Leukemia

• Sponsor: Rutgers, The State University of New Jersey (Other)
• Overall Status: Completed
• CT.gov ID: NCT00176462
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 60
• Locations: 2
• Arms: 2
• Duration (Months): 91
• Patients Per Site: 30
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this research study is to identify better ways to treat children and young adults with acute lymphocytic leukemia (ALL). At the same time, doctors hope to define methods to identify those patients at higher risk for certain side effects, as well as those who are at higher risk for relapse of their leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphocytic Leukemia	Drug: aminopterin; Drug: L-asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunomycin; Drug: dexamethasone; Drug: 6-mercaptopurine; Drug: methotrexate; Drug: 6-thioguanine; Drug: vincristine; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone); Drug: Leucovorin	Phase 2

Detailed Description

Outline of Therapy:

Combinations of chemotherapy drugs will be given orally, intravenously and intrathecally (directly into the cerebrospinal fluid by spinal tap) over a period of roughly two and a half years.

Therapy will be divided into five phases:

Induction (4 weeks): chemotherapy given to produce a clinical remission (defined by normal blood counts, with the absence of leukemia cells in the blood and fewer than 5% leukemia cells in the bone marrow).

Consolidation (11 weeks): chemotherapy given to consolidate the remission. Delayed Intensification (7 weeks) Intensive chemotherapy aimed at killing any resistant leukemia cells will be given only for patients at high risk of relapse.

Intensive Continuation (approximately 1 year): Eight week cycles of chemotherapy, given eight times.

Continuation (final year of therapy): Eight week cycles of largely oral chemotherapy, with one clinic visit for a lumbar puncture every eight weeks.

Irradiation: radiation will be given in the middle of intensive continuation to the head and spine of those patients who have leukemia cells found in the cerebrospinal fluid at the time of diagnosis.

Follow-up: After the conclusion of therapy, there will be periodic office visits, initially monthly, then gradually spaced out to annual visits. The purpose of these visits is to evaluate for late side-effects of therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: CINJALL: Treatment for Children With Acute Lymphocytic Leukemia
• Study Start Date: Feb 1, 2001
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Standard Risk 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin	Drug: L-asparaginase; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: daunomycin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: dexamethasone; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-mercaptopurine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: methotrexate; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: vincristine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone); Drug: Leucovorin
Experimental: Arm 2 High Risk 6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C	Drug: aminopterin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: L-asparaginase; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: cyclophosphamide; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: cytarabine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: daunomycin; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: dexamethasone; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-mercaptopurine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: 6-thioguanine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: vincristine; Therapy will be divided into five phases: Induction, Consolidation, Delayed Intensification (only for those patients meeting clinical criteria defining a high risk of relapse), Intensive Continuation, and Continuation; Drug: Triple Intrathecal Therapy (MTX, Cytarabine, Hydrocortisone); Drug: Leucovorin

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years [5 years]

   This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission.

Secondary Outcome Measures

1. To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion:

• Newly Diagnosed ALL, excluding mature B-cell ALL (surface Ig positive)

• Patients with overt CNS (central nervous system) or testicular disease are eligible

• Informed consent according to institutional and FDA guidelines.

• Adequate organ function is required.

• HIV seropositive patients will not be excluded from this study.

• Patients greater than 1 year of age and less than 29.99 years of age are eligible.

Exclusion Criteria

• Patients with medical, psychological, or psychiatric problems that are likely to compromise their ability to tolerate intensive therapy will be ineligible.

• All patients with evidence of significant organ dysfunction not thought to be attributable to ALL (patients with clinically significant congestive heart failure, cardiac ejection fraction <40%, total bilirubin >2, serum creatinine >2) will be ineligible. Note: echocardiogram or MUGA are required prior to therapy ONLY for those patients with history or physical findings suggestive of cardiac dysfunction not directly attributable to anemia or ALL. Note: Patients with total bilirubin >2 but direct (conjugated) bilirubin less than the upper limit of normal will still be eligible. These patients should be evaluated for deficiency of the enzyme glucuronyl transferase.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jersey Shore University Medical Center	Neptune	New Jersey	United States	07754
2	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903

Sponsors and Collaborators

• Rutgers, The State University of New Jersey
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Barton Kamen, MD, Rutgers, The State University of New Jersey

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Rutgers, The State University of New Jersey
• ClinicalTrials.gov Identifier: NCT00176462
• Other Study ID Numbers: 020101; 0220003389; P30CA072720
• First Posted: Sep 15, 2005
• Last Update Posted: Jun 9, 2014
• Last Verified: May 1, 2014

• Keywords provided by Rutgers, The State University of New Jersey: Acute Lymphocytic Leukemia; Leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leucovorin; Cytarabine; Dexamethasone; Hydrocortisone; Cyclophosphamide; Methotrexate; Vincristine; Asparaginase; Mercaptopurine; Thioguanine; Daunorubicin; Aminopterin

Study Results

Participant Flow

Recruitment Details	59 patients with ALL were enrolled between March, 2001 and September, 2005 at the Cancer Institute of New Jersey (outpatient clinical research facility) and 1 patient was enrolled at Jersey Shore University Medical Center (a community hospital).

Arm/Group Title	Arm 1 Standard Risk	Arm 2 High Risk
Arm/Group Description	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C
Period Title: Induction (4 Weeks)
STARTED	21	39
COMPLETED	20	34
NOT COMPLETED	1	5
Period Title: Induction (4 Weeks)
STARTED	20	34
COMPLETED	20	29
NOT COMPLETED	0	5
Period Title: Induction (4 Weeks)
STARTED	20	29
COMPLETED	20	29
NOT COMPLETED	0	0
Period Title: Induction (4 Weeks)
STARTED	20	29
COMPLETED	19	26
NOT COMPLETED	1	3
Period Title: Induction (4 Weeks)
STARTED	19	26
COMPLETED	19	26
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm 1 Standard Risk	Arm 2 High Risk	Total
Arm/Group Description	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C	Total of all reporting groups
Overall Participants	21	39	60
Age (Count of Participants)
<=18 years	21 100%	30 76.9%	51 85%
Between 18 and 65 years	0 0%	9 23.1%	9 15%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	3.71 (1.77)	16 (9.8)	11.7 (9.89)
Sex: Female, Male (Count of Participants)
Female	11 52.4%	18 46.2%	29 48.3%
Male	10 47.6%	21 53.8%	31 51.7%
Region of Enrollment (participants) [Number]
United States	21 100%	39 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With ALL at High Risk of Relapse (Arm 2) Who Were Relapse-free at 5 Years
Description	This measure looks at the percentage of patients on Arm 2 who did not experience a relapse at 5 years, where relapse is defined as the presence of progressive disease after the achievement of a complete remission.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Number of high risk ALL patients treated.

Arm/Group Title	Arm 2 High Risk
Arm/Group Description	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C
Measure Participants	37
Number [percentage of participants]	64.9 309%

2. Secondary Outcome

Title	To Measure 5-methyltetrahydrofolate, Aminopterin and Methotrexate Uptake in Leukemic Blasts Isolated at Diagnosis
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

We did not analyze this outcome measure. The laboratory analysis was not performed. The Principal Investigator left the institution.

Arm/Group Title	Arm 1 Standard Risk	Arm 2 High Risk
Arm/Group Description	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C
Measure Participants	0	0

Adverse Events

Time Frame	7 years, 6 months
Arm/Group Title	Arm 1 Standard Risk		Arm 2 High Risk
Arm/Group Description	6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE METHOTREXATE Leucovorin		6-MERCAPTOPURINE DAUNOMYCIN DEXAMETHASONE Triple Intrathecal Therapy (ITT) L-ASPARAGINASE VINCRISTINE 6-THIOGUANINE CYTARABINE AMINOPTERIN CYCLOPHOSPHAMIDE ARABINOSIDE-C
All Cause Mortality
	Arm 1 Standard Risk		Arm 2 High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1 Standard Risk		Arm 2 High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/21 (95.2%)		36/39 (92.3%)
Blood and lymphatic system disorders
Platelets	5/21 (23.8%)	5	5/39 (12.8%)	7
Hypokalemia	0/21 (0%)	0	1/39 (2.6%)	1
Hemoglobin	1/21 (4.8%)	1	3/39 (7.7%)	4
Fibrinogen	0/21 (0%)	0	1/39 (2.6%)	1
Leukocytes (total WBC) - Neutropenia	0/21 (0%)	0	3/39 (7.7%)	4
Hyperglycemia	0/21 (0%)	0	2/39 (5.1%)	2
Hyperbilirubinemia	0/21 (0%)	0	1/39 (2.6%)	1
Hypoalbuminemia	0/21 (0%)	0	1/39 (2.6%)	1
Neutrophils/granulocytes (ANC/AGC)	1/21 (4.8%)	1	0/39 (0%)	0
Cardiac disorders
Cardiac troponin I	0/21 (0%)	0	1/39 (2.6%)	1
Gastrointestinal disorders
Dehydration	0/21 (0%)	0	3/39 (7.7%)	3
Vomiting	0/21 (0%)	0	2/39 (5.1%)	2
Abdominal pain or cramping	0/21 (0%)	0	1/39 (2.6%)	1
Stomatitis / pharyngitis	0/21 (0%)	0	2/39 (5.1%)	3
Pancreatitis	1/21 (4.8%)	1	1/39 (2.6%)	1
Typhlitis (inflammation of cecum)	0/21 (0%)	0	2/39 (5.1%)	2
Diarrhea	0/21 (0%)	0	1/39 (2.6%)	1
General disorders
Thrombosis/embolism	1/21 (4.8%)	1	1/39 (2.6%)	1
Fever	1/21 (4.8%)	1	1/39 (2.6%)	2
Anorexia	0/21 (0%)	0	3/39 (7.7%)	3
Fatigue	0/21 (0%)	0	1/39 (2.6%)	1
Syncope	0/21 (0%)	0	2/39 (5.1%)	2
Infections and infestations
Febrile neutropenia	16/21 (76.2%)	29	17/39 (43.6%)	35
Infection with unknown ANC	1/21 (4.8%)	1	3/39 (7.7%)	3
Infection (documented clinically or microbiologically) with grade 3 or 4 neutropenia	1/21 (4.8%)	1	2/39 (5.1%)	2
Infection without neutropenia	3/21 (14.3%)	3	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness (not due to neuropathy)	0/21 (0%)	0	5/39 (12.8%)	7
Joint pain	0/21 (0%)	0	1/39 (2.6%)	1
Muscle Pain	0/21 (0%)	0	1/39 (2.6%)	1
Bone pain	0/21 (0%)	0	1/39 (2.6%)	1
Osteonecrosis	0/21 (0%)	0	1/39 (2.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Relapsed leukemia	0/21 (0%)	0	1/39 (2.6%)	1
Nervous system disorders
Neurology	1/21 (4.8%)	1	0/39 (0%)	0
Neuropathy	0/21 (0%)	0	2/39 (5.1%)	2
Neuropathic pain	0/21 (0%)	0	1/39 (2.6%)	1
Psychiatric disorders
Psychosis	1/21 (4.8%)	1	0/39 (0%)	0
Renal and urinary disorders
Melena/GI bleeding - Hemorrhage	0/21 (0%)	0	1/39 (2.6%)	1
Renal failure	0/21 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/21 (9.5%)	2	1/39 (2.6%)	1
Pneumonitis/pulmonary infiltrates	3/21 (14.3%)	4	2/39 (5.1%)	2
Cough	0/21 (0%)	0	1/39 (2.6%)	1
Broncohspasm	0/21 (0%)	0	1/39 (2.6%)	1
Hypoxia	0/21 (0%)	0	1/39 (2.6%)	1
Pleural effusion	0/21 (0%)	0	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders
Allergic reaction/hypersensitivity	0/21 (0%)	0	2/39 (5.1%)	2
Rash/desquamation	0/21 (0%)	0	1/39 (2.6%)	1
Vascular disorders
DIC (disseminated intravascular coagulation)	0/21 (0%)	0	2/39 (5.1%)	2
Other (Not Including Serious) Adverse Events
	Arm 1 Standard Risk		Arm 2 High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/21 (100%)		39/39 (100%)
Blood and lymphatic system disorders
Platelets	1/21 (4.8%)	1	3/39 (7.7%)	4
Pancytopenia	0/21 (0%)	0	3/39 (7.7%)	4
Hypokalemia	1/21 (4.8%)	1	0/39 (0%)	0
Hemoglobin	2/21 (9.5%)	3	0/39 (0%)	0
Hyperammonemia	0/21 (0%)	0	1/39 (2.6%)	1
Hyperglycemia	0/21 (0%)	0	1/39 (2.6%)	1
Hypercalcemia	0/21 (0%)	0	1/39 (2.6%)	1
Hyperbilirubinemia	0/21 (0%)	0	2/39 (5.1%)	2
Cardiac disorders
Tachycardia	0/21 (0%)	0	1/39 (2.6%)	1
Ventricular arrythmia	0/21 (0%)	0	1/39 (2.6%)	1
Hypotension	1/21 (4.8%)	1	1/39 (2.6%)	1
Ear and labyrinth disorders
Otitis middle ear	0/21 (0%)	0	1/39 (2.6%)	1
Gastrointestinal disorders
Dehydration	1/21 (4.8%)	1	5/39 (12.8%)	6
Nausea	0/21 (0%)	0	3/39 (7.7%)	9
Vomiting	2/21 (9.5%)	2	7/39 (17.9%)	17
Gastritis	0/21 (0%)	0	1/39 (2.6%)	1
Abdominal pain or cramping	1/21 (4.8%)	1	4/39 (10.3%)	4
Stomatitis / pharyngitis	1/21 (4.8%)	1	4/39 (10.3%)	5
Appendicitis	0/21 (0%)	0	1/39 (2.6%)	1
Bowel obstruction	0/21 (0%)	0	1/39 (2.6%)	1
Pancreatitis	0/21 (0%)	0	1/39 (2.6%)	1
Weight gain	1/21 (4.8%)	1	0/39 (0%)	0
GI other (Elevated liver enzymes)	1/21 (4.8%)	1	0/39 (0%)	0
Diarrhea	0/21 (0%)	0	1/39 (2.6%)	2
Excessive thirst	0/21 (0%)	0	1/39 (2.6%)	1
Amylase	0/21 (0%)	0	1/39 (2.6%)	1
General disorders
Fever	12/21 (57.1%)	22	15/39 (38.5%)	21
Headache - Pain-Head	0/21 (0%)	0	7/39 (17.9%)	10
Other Toxicity	3/21 (14.3%)	3	5/39 (12.8%)	5
Chest pain	0/21 (0%)	0	1/39 (2.6%)	1
Pain	0/21 (0%)	0	2/39 (5.1%)	2
Rigors	0/21 (0%)	0	1/39 (2.6%)	2
Immune system disorders
Allergic reaction/hypersensitivity	3/21 (14.3%)	4	0/39 (0%)	0
Infections and infestations
Infection with unknown ANC	1/21 (4.8%)	1	4/39 (10.3%)	4
Infection without neutropenia	1/21 (4.8%)	1	1/39 (2.6%)	1
Infection / Febrile neutropenia	1/21 (4.8%)	1	0/39 (0%)	0
Musculoskeletal and connective tissue disorders
Extremity pain	0/21 (0%)	0	2/39 (5.1%)	2
Joint pain	0/21 (0%)	0	1/39 (2.6%)	1
Muscle Pain	0/21 (0%)	0	2/39 (5.1%)	2
Fracture	0/21 (0%)	0	1/39 (2.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ascites	0/21 (0%)	0	1/39 (2.6%)	1
Nervous system disorders
Neuropathy	0/21 (0%)	0	3/39 (7.7%)	3
Speech impairment	0/21 (0%)	0	1/39 (2.6%)	3
Seizure(s)	0/21 (0%)	0	1/39 (2.6%)	2
Neurology - Mood Alteration	0/21 (0%)	0	1/39 (2.6%)	1
Renal and urinary disorders
Urinary freqency	0/21 (0%)	0	1/39 (2.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/21 (0%)	0	2/39 (5.1%)	2
Rhinitis	0/21 (0%)	0	1/39 (2.6%)	1
Upper respiratory infection	0/21 (0%)	0	1/39 (2.6%)	1
Edema (Pulmonary)	1/21 (4.8%)	2	0/39 (0%)	0
Tachypnea	1/21 (4.8%)	1	0/39 (0%)	0
Pneumothorax	0/21 (0%)	0	1/39 (2.6%)	1
Wheezing	0/21 (0%)	0	1/39 (2.6%)	1
Fever & pneumonia	1/21 (4.8%)	1	0/39 (0%)	0
Skin and subcutaneous tissue disorders
Rash/desquamation	1/21 (4.8%)	1	1/39 (2.6%)	1
Phlebitis (superficial)	0/21 (0%)	0	1/39 (2.6%)	1
Vascular disorders
Cerebrovascular accident	0/21 (0%)	0	1/39 (2.6%)	1

Limitations/Caveats

Antifolate therapy was non-randomly assigned, therefore, we do not have a statistical basis to compare the toxicity observed among patients on the standard risk and high risk treatment arms.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.