Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00882206
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arm: 1
• Duration (Months): 45
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Decitabine and vorinostat may alter the cancer cells by reversing the cancer pathways needed for cell growth. Giving more than one drug (combination chemotherapy) together with decitabine and vorinostat may kill more cancer cells than with chemotherapy alone.

PURPOSE: This phase II trial is studying how well giving decitabine and vorinostat together with combination chemotherapy works in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma that has relapsed or not responded to treatment.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma	Drug: cytarabine; Drug: decitabine; Drug: doxorubicin hydrochloride; Drug: imatinib mesylate; Drug: methotrexate; Drug: pegaspargase; Drug: prednisone; Drug: vincristine sulfate; Drug: vorinostat	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies. Samples are analyzed for hypermethylation at diagnosis and demethylation post-exposure with decitabine and vorinostat using LINE methylation.

OUTLINE:

Patients receive decitabine IV over 1 hour and oral vorinostat twice daily on days 1-4; vincristine sulfate IV on days 5, 12, 19, and 26; oral prednisone twice daily on days 5-33; doxorubicin hydrochloride IV over 15 minutes and cytarabine intrathecally (IT) on day 5; pegaspargase IV or intramuscularly on days 6, 12, 19, and 26; and methotrexate* IT on days 12 and 33. Patients with Philadelphia chromosome-positive disease may also receive oral imatinib mesylate once daily on days 5-33.

NOTE: *Patients with central nervous system (CNS)-positive disease also receive methotrexate IT on days 19 and 26.

Patients undergo blood and bone marrow sample collection at baseline, on day 5, Day 19 and at the end of study treatment for correlative laboratory studies.

After completion of study treatment, patients are followed for 60 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Therapeutic Trial of Decitabine and Vorinostat in Combination With Chemotherapy (Vincristine, Prednisone, Doxorubicin and PEG-Asparaginase) for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL)
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Decitabine / Vorinostat This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.

Drug: cytarabine; At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.; Other Names: cytosine arabinoside ; Drug: decitabine; Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour; Other Names: Dacogen(R) ; Drug: doxorubicin hydrochloride; Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes; Other Names: Doxorubicin ; Drug: imatinib mesylate; 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33.; Other Names: Gleevec(R) ; Drug: methotrexate; **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.; Other Names: MTX ; Drug: pegaspargase; 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26); Other Names: PEG asparaginase ; Drug: prednisone; 40mg/m2/day divided BID (days 5 - 33); Drug: vincristine sulfate; 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12, 19, 26); Other Names: Oncovin(R) ; Drug: vorinostat; Days 1-4, (230 mg/m2)orally divided twice a day (max dose 400 mg daily); Other Names: suberoylanilide hydroxamic acid (SAHA)

Outcome Measures

Primary Outcome Measures

1. Response to Treatment [Day 33]

   Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)

Secondary Outcome Measures

1. Level of Methylation [Day 0]

   the percentage of methylated DNA

2. Level of Methylation [Day 5]

   the percentage of methylated DNA

3. Level of Methylation [Day 33]

   the percentage of methylated DNA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of lymphoblastic lymphoma or acute lymphoblastic leukemia with ≥ 5% blasts in the bone marrow (M2/M3) (with or without extramedullary disease) that meets 1 of the following criteria:

• Refractory disease/induction failure (failure to achieve initial remission after 2 lines of induction therapy)

• Relapsed disease (in first relapse or higher)

• Central nervous system (CNS)-positive disease allowed

• Karnofsky performance status (PS) 50-100% (for patients ≥ 16 years of age) OR Lansky PS 50-100% (for patients < 16 years of age)

• Life expectancy ≥ 8 weeks

• Creatinine clearance ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:

• 0.4 mg/dL (for patients 1 to 5 months of age)

• 0.5 mg/dL (for patients 6 to 11 months of age)

• 0.6 mg/dL (for patients 1 year of age)

• 0.8 mg/dL (for patients 2 to 5 years of age)

• 1.0 mg/dL (for patients 6 to 9 years of age)

• 1.2 mg/dL (for patients 10 to 12 years of age)

• 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

• 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

• ALT < 5 times upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 times ULN for age

• LVEF ≥ 40% by ECHO/MUGA scan

• Shortening fraction > 29% by ECHO/MUGA scan

• Able to swallow capsules

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 2 months after completion of study treatment

• No untreated positive blood cultures or progressive infections as assessed by radiographic studies

• No known allergy to any of the agents or their ingredients used in this study

• Patients with clinically significant prior allergies to pegaspargase may be treated with asparaginase-Erwinia, if available

• Patients who cannot receive asparaginase on this study (e.g., due to prior pancreatitis, stroke, or other toxicity) are eligible provided they meet all other inclusion/exclusion criteria

• Recovered from prior therapy (defined as CTCAE v3.0 toxicity ≤ grade 1)

• More than 3 weeks since prior chemotherapy for cancer other than hydroxyurea for patients with WBC > 10,000/mm³

• At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)

• At least 1 month since prior biologic therapy, such as monoclonal antibodies

• At least 3 months since prior hematopoietic stem cell transplantation

Exclusion Criteria:

• Evidence of graft-versus-host disease

• Concurrent valproic acid

• Concurrent coumadin/warfarin other than a short course administered in a prophylactic setting

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota Amplatz Children's Hospital	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Michael J. Burke, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00882206
• Other Study ID Numbers: 2008LS112; 0810M50401; MT2008-29R
• First Posted: Apr 16, 2009
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: recurrent adult lymphoblastic lymphoma; recurrent childhood lymphoblastic lymphoma; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia
• Additional relevant MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Cytarabine; Prednisone; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Imatinib Mesylate; Decitabine; Asparaginase; Vorinostat; Pegaspargase

Study Results

Participant Flow

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy. cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg. decitabine: Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour doxorubicin hydrochloride: Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33. methotrexate: **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg. pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26) prednisone: 40mg/m2/day divided BID (days 5 - 33) vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12,
Period Title: Overall Study
STARTED	13
COMPLETED	13
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
Overall Participants	13
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	16
Sex: Female, Male (Count of Participants)
Female	4 30.8%
Male	9 69.2%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Response to Treatment
Description	Response includes both complete remission (defined as <5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
Time Frame	Day 33

Outcome Measure Data

Analysis Population Description

The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
Measure Participants	8
Number [participants]	6 46.2%

2. Secondary Outcome

Title	Level of Methylation
Description	the percentage of methylated DNA
Time Frame	Day 0

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy. cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg. decitabine: Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour doxorubicin hydrochloride: Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33. methotrexate: **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg. pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26) prednisone: 40mg/m2/day divided BID (days 5 - 33) vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12,
Measure Participants	8
Mean (Standard Deviation) [percentage of DNA]	84.98 (1.48)

3. Secondary Outcome

Title	Level of Methylation
Description	the percentage of methylated DNA
Time Frame	Day 5

Outcome Measure Data

Analysis Population Description

The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy. cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg. decitabine: Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour doxorubicin hydrochloride: Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33. methotrexate: **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg. pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26) prednisone: 40mg/m2/day divided BID (days 5 - 33) vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12,
Measure Participants	8
Mean (Standard Deviation) [percentage of DNA]	79.82 (3.04)

4. Secondary Outcome

Title	Level of Methylation
Description	the percentage of methylated DNA
Time Frame	Day 33

Outcome Measure Data

Analysis Population Description

The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy. cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg. decitabine: Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour doxorubicin hydrochloride: Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33. methotrexate: **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg. pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26) prednisone: 40mg/m2/day divided BID (days 5 - 33) vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12,
Measure Participants	8
Mean (Standard Deviation) [percentage of DNA]	86.1 (1.87)

Adverse Events

Arm/Group Title	Decitabine / Vorinostat
Arm/Group Description	This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy. cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed. *Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg. decitabine: Days 1-4, 15 mg/m^2 intravenously (IV) over 1 hour doxorubicin hydrochloride: Day 5, 60 mg/m^2 intravenously (IV) over 15 minutes imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age <18 years and 400 mg orally every day for >18 years on Days 5-33. methotrexate: **Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg. pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26) prednisone: 40mg/m2/day divided BID (days 5 - 33) vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12)
All Cause Mortality
	Decitabine / Vorinostat
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Decitabine / Vorinostat
	Affected / at Risk (%)	# Events
Total	8/13 (61.5%)
Blood and lymphatic system disorders
Febrile neutropenia	2/13 (15.4%)
Gastrointestinal disorders
Pancreatitis	2/13 (15.4%)
Pain, abdominal	1/13 (7.7%)
Infections and infestations
Infection, blood	6/13 (46.2%)
Investigations
Lipase elevated	1/13 (7.7%)
Metabolism and nutrition disorders
Hypertriglyceridemia	1/13 (7.7%)
Hyponatremia	1/13 (7.7%)
Hyperglycemia	1/13 (7.7%)
Hypercholesteremia	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Pain, generalized body	1/13 (7.7%)
Nervous system disorders
Cerebral hemorrhage	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/13 (7.7%)
Decreased respiratory rate	1/13 (7.7%)
Hypoxia - acute respiratory distress	1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	Decitabine / Vorinostat
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Hemorrhage, bladder	1/13 (7.7%)
Leukocytes decreased	3/13 (23.1%)
Anemia	6/13 (46.2%)
Platelets count decreased	3/13 (23.1%)
Neutrophil count decreased	1/13 (7.7%)
Lymphopenia	1/13 (7.7%)
Platelets	2/13 (15.4%)
Bone marrow cellularity	1/13 (7.7%)
Febrile neutropenia	6/13 (46.2%)
Leukocytes	2/13 (15.4%)
Neutrophils	1/13 (7.7%)
ANC	1/13 (7.7%)
Cardiac disorders
Tachycardia	2/13 (15.4%)
Hypertension	2/13 (15.4%)
Ventricular arrythmia	1/13 (7.7%)
Systolic murmur	1/13 (7.7%)
Sinus tachycardia	1/13 (7.7%)
Hypotension	1/13 (7.7%)
Endocrine disorders
Adrenal insufficiency	1/13 (7.7%)
Eye disorders
Photophobia	1/13 (7.7%)
Blurred vision	1/13 (7.7%)
Gastrointestinal disorders
Nausea	4/13 (30.8%)
Constipation	5/13 (38.5%)
Diarrhea	3/13 (23.1%)
Vomiting	1/13 (7.7%)
Pancreatitis	1/13 (7.7%)
Fluid retention, ascites	1/13 (7.7%)
Lower molar pain	1/13 (7.7%)
Abdominal pain	6/13 (46.2%)
Mucositis	4/13 (30.8%)
General disorders
Fatigue	4/13 (30.8%)
Edema, lower extremity	2/13 (15.4%)
Edema, upper extremity	1/13 (7.7%)
Generalised body aches	1/13 (7.7%)
Weakness	1/13 (7.7%)
Fever	2/13 (15.4%)
Infections and infestations
Infection, meningitis	1/13 (7.7%)
Fungal infection, lung	1/13 (7.7%)
Infection, soft tissue	1/13 (7.7%)
Infection, neutopenia	2/13 (15.4%)
Infection, positive blood culture	1/13 (7.7%)
Injury, poisoning and procedural complications
Pain uncontrolled	1/13 (7.7%)
Pain, epigastric	1/13 (7.7%)
Pain, headache	1/13 (7.7%)
Pain, pedal bilateral	1/13 (7.7%)
Pain, leg bilateral	2/13 (15.4%)
Pain, stomach	1/13 (7.7%)
Pain, left chest	1/13 (7.7%)
Pain, low back/leg	1/13 (7.7%)
Lower lip swelling	1/13 (7.7%)
Pain, NOS	1/13 (7.7%)
Investigations
Hyperbilirubinemia	4/13 (30.8%)
Weight gain	1/13 (7.7%)
Creatinine	1/13 (7.7%)
Lipase elevated	1/13 (7.7%)
Alkaline phosphatase increased	2/13 (15.4%)
ALT increased	4/13 (30.8%)
Creatinine increased	2/13 (15.4%)
Fibrinogen increased	1/13 (7.7%)
Amylase	1/13 (7.7%)
Lipase	1/13 (7.7%)
Hypomagnesemia	1/13 (7.7%)
AST increased	1/13 (7.7%)
AST	1/13 (7.7%)
Metabolism and nutrition disorders
Hypermagnesemia	2/13 (15.4%)
Hyponatremia	2/13 (15.4%)
Hyperglycemia	5/13 (38.5%)
Hyperchloremia	1/13 (7.7%)
Hypertriglyceridemia	1/13 (7.7%)
Albumin	2/13 (15.4%)
Calcium	2/13 (15.4%)
Glucose	1/13 (7.7%)
Hypokalemia	5/13 (38.5%)
Hyperkalemia	1/13 (7.7%)
Hypoalbuminemia	3/13 (23.1%)
Dehydration	1/13 (7.7%)
Anorexia	1/13 (7.7%)
Uric acid increased	1/13 (7.7%)
Calcium decreased	2/13 (15.4%)
Hyperphosphatemia	2/13 (15.4%)
Calcium increased	1/13 (7.7%)
Obesity	1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Knee pain	1/13 (7.7%)
Back pain	1/13 (7.7%)
Hip pain	1/13 (7.7%)
Nervous system disorders
Somnolence	2/13 (15.4%)
Headaches	2/13 (15.4%)
Hemiparesis, right side	1/13 (7.7%)
Neuropathy	4/13 (30.8%)
Psychiatric disorders
Mood alteration, NOS	1/13 (7.7%)
Depression	2/13 (15.4%)
Anxiety	3/13 (23.1%)
Insomnia	1/13 (7.7%)
Confusion	1/13 (7.7%)
Renal and urinary disorders
Chronic kidney disease	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	2/13 (15.4%)
Sleep apnea	1/13 (7.7%)
Pleural effusion	1/13 (7.7%)
Pulmonary infiltrate	1/13 (7.7%)
Dyspnea	3/13 (23.1%)
Skin and subcutaneous tissue disorders
Hand foot reaction	1/13 (7.7%)
Demi Erythema	1/13 (7.7%)
Alopecia	2/13 (15.4%)
Ulceration, decubitus	1/13 (7.7%)
Rash	1/13 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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