Tandem Auto-Allo Transplant for Lymphoma | NCT01181271

NCT01181271

Name	Class
Dana-Farber Cancer Institute	OTHER

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Autologous then Allogeneic transplant	Experimental	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).	Drug: Busulfan (conditioning for AUTO transplant) Drug: Etoposide (conditioning for AUTO transplant) Drug: Cyclophosphamide (conditioning for AUTO transplant) Drug: Mesna (prior to AUTO transplant) Other: autologous (auto) peripheral blood stem cell transplantation Drug: Neupogen Drug: Fludarabine (conditioning for ALLO Transplant) Drug: Busulfan (conditioning for ALLO Transplant) Other: non-myeloablative allogeneic (allo) transplant Drug: Tacrolimus Drug: Sirolimus Drug: Methotrexate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Busulfan (conditioning for AUTO transplant)	Drug	0.8 mg/kg intravenous (IV) bolus every six hours (Q6H) on days -8,-7,-6,-5 (total of 14 doses). The total daily dose of busulfan will be 3.2 mg/kg on days -8,-7, and -6 and 1.6 mg/kg on day -5

Measure	Description	Time Frame
Peripheral Blood All-cell Donor Chimerism	Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.	100 days post allogeneic transplant

Measure	Description	Time Frame
Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL		within 28 days after allogeneic transplant
Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)	Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients with high-risk diffuse large B cell or transformed low grade lymphoma defined as:
- Residual disease after at least 6 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
- Progressive disease after at least 2 cycles of anthracycline-based chemotherapy
- Patients with an initial complete response but subsequent relapse within 6 months after completion of anthracycline-based chemotherapy
Patients with any T-cell non-Hodgkin's lymphoma as defined as:
- Peripheral T-cell lymphoma (ALK negative PTCL-U) including PTCL-NOS, HSGD (hepato-splenic gamma-delta TCL), AITL (angioimmunoblastic T-cell lymphoma), EATL (enteropathy associated T-cell lymphoma), ALK-negative anaplastic large cell lymphoma
- Any T-cell histology (except LGL) with residual disease after at least 4 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
Patients with mantle cell lymphoma at any time in therapy
Patients with "double-hit" lymphoma as characterized by the presence of concurrent overexpression of Bcl-2 and c-myc
Patients with Hodgkin's lymphoma that is
- Refractory to first-line therapy and at least one second line chemotherapy regimen
- Relapsed Hodgkin's lymphoma which is refractory to at least one salvage chemotherapy regimen.
Patients with CLL/SLL with 17p- cytogenetic abnormality
Age 18 years and greater
ECOG performance status 0-2
Ability to understand and the willingness to sign a written informed consent document.
Responsive disease to last therapy as determined by at least one of the following:
- At least PR by Revised Response Criteria
- At least PR by traditional Cheson Criteria
- < 10% of overall cellularity involved with disease on bone marrow biopsy for patients with involvement of the bone marrow
Minimum of 2 x 106 CD34+ cells / kg already collected and frozen. These stem cells may have been collected from PBSC pheresis, bone marrow harvest, or the combination.

Exclusion Criteria:

Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative transplant

Pregnancy
Evidence of HIV infection
Heart failure uncontrolled by medications or ejection fraction less than 45%
Active involvement of the CNS by lymphoma
Inability to provide informed consent
Previous autologous or allogeneic stem cell transplant
Creatinine greater than 2 gm/dL or 24 hour urine creatinine clearance < 50 cc/minute (does not have to satisfy both)
Total bilirubin greater than 2 times the upper limit of normal except when due to Gilbert's syndrome or hemolysis.
Transaminases greater than 3 times the upper limit of normal
FVC or DLCO of less than 50% of predicted (DLCO corrected for hemoglobin level)
Already known to not possess suitably HLA-matched related or unrelated donor

Eligibility to proceed to allogeneic transplant Cannot be admitted for allogeneic transplant earlier than 40 days and no later than 180 days after autologous stem cell transplant.

HLA identical (A, B, C and DR) related or unrelated donor available. HLA typing of class I loci (HLA- A, B, C) will be based on complement dependent cytotoxicity assay or PCR of sequence specific oligonucleotide primers (SSOP). Typing of HLA class II (DRB1) will be based on PCR of sequence specific oligonucleotide primers (SSOP).
No need for intravenous hydration in the previous 2 weeks
Resolved mucositis
Renal, cardiac, pulmonary, and hepatic function meet standard criteria for nonmyeloablative SCT as listed below:
- Serum Cr < 2 gm/dL
- LV ejection fraction > 30% and no uncontrolled symptoms of congestive heart failure
- DLCO > 50% of predicted value (corrected for hemoglobin)
- Transaminases < 5X the institution upper limit of normal
- Bilirubin < 3X the institution upper limit of normal except when Gilbert's Syndrome or hemolysis is present
- ECOG PS ≤ 2
No intravenous antimicrobials within 2 weeks
No evidence of progressive disease, defined as a 25% increase from nadir in the sum of the product of the diameters (SPD) of any lymph node previously identified as abnormal prior to autologous transplant or the appearance of any new lymph node greater than 1.5 cm in greatest diameter, new bone marrow involvement, or new solid organ nodule greater than 1 cm in diameter. This restaging study will be performed at least 28 days after the autologous transplant and within 60 days prior to admission for allogeneic transplant. Status of stable disease (SD) is acceptable to proceed to allogeneic transplant.

Name	Affiliation	Role
Yi-Bin A Chen, MD	Massachusetts General Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Massachusetts General Hospital		Boston	Massachusetts	02114	United States
Dana Farber Cancer Institute

PubMed Identifier	Type	Citation	Retractions
26009261	Result	Chen YB, Li S, Fisher DC, Driscoll J, Del Rio C, Abramson J, Armand P, Barnes J, Brown J, Cutler C, El-Jawahri A, Ho VT, Hochberg E, McAfee S, Takvorian R, Spitzer TR, Antin JH, Soiffer R, Jacobsen E. Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma. Biol Blood Marrow Transplant. 2015 Sep;21(9):1583-8. doi: 10.1016/j.bbmt.2015.05.016. Epub 2015 May 22.

ID	Title	Description
FG000	Autologous Then Allogeneic Transplant	Autologous, then Allogeneic Stem Cell Transplantation

ID	Title	Description
BG000	Autologous Then Allogeneic Transplant	Autologous then allogeneic stem cell transplantation

Units	Counts
Participants	BG00042

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Peripheral Blood All-cell Donor Chimerism

Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.

Participants who underwent the full tandem AUTO-ALLO stem cell transplant

Posted

Median

Full Range

percentage of donor-derived elements

100 days post allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG00029

Title

Denominators

Categories

Title	Measurements
	OG00095(83 to 99)

Secondary

Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL

This was only measured in the 17 participants who experienced a hematological nadir after allo transplant.

Posted

Median

Full Range

days

within 28 days after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Posted

Number

90% Confidence Interval

percentage of participants

within 200 days after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Cumulative Incidence of Extensive Chronic Graft-versus-host-disease

Extensive chronic graft versus-host-disease (GVHD) was defined as GVHD that required systemic immunosuppression.

Posted

Number

90% Confidence Interval

percentage of participants

1-year after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Cumulative Incidence of Non-relapse Mortality

Non-relapse mortality is defined as participants who die from causes other than their underlying disease relapse, such as infection or graft versus host disease

Posted

Number

90% Confidence Interval

percentage of participants

2-years after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Cumulative Incidence of Disease Relapse

Posted

Number

90% Confidence Interval

percentage of participants

2-years after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Progression Free Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

Posted

Number

90% Confidence Interval

percentage of participants

2 years after allogeneic transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Overall Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

Posted

Number

90% Confidence Interval

percentage of participants

Two-years after Allogeneic Transplant

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Progression Free Survival Rate for All Participants

Posted

Number

90% Confidence Interval

percentage of participants

2 years

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Overall Survival Rate for All Participants

Posted

Number

90% Confidence Interval

percentage of participants

2 years

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Progression Free Survival Rate for Participants Undergoing Only Autologous Transplant

Participants who ONLY underwent Autologous transplant (did not proceed to Allogeneic)

Posted

Number

90% Confidence Interval

percentage of participants

Two Years

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Secondary

Estimated Two Year Overall Survival Rate for Participants Undergoing Only Autologous Transplant

Participants who ONLY underwent Autologous transplant, did not proceed to Allogeneic transplant

Posted

Number

90% Confidence Interval

percentage of participants

two years

ID	Title	Description
OG000	Autologous Then Allogeneic Transplant	All patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
anemia	Blood and lymphatic system disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected42 at risk
febrile neutropenia	Blood and lymphatic system disorders	CTCAE (4.0)	Non-systematic Assessment	EG0005 affected42 at risk
colitis	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0002 affected42 at risk
diarrhea	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected42 at risk
mucositis oral	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected42 at risk
nausea	Gastrointestinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0003 affected42 at risk
edema	General disorders	CTCAE (4.0)	Non-systematic Assessment	EG0002 affected42 at risk
neutrophil count decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG0002 affected42 at risk
platelet count decreased	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG0006 affected42 at risk
weight loss	Investigations	CTCAE (4.0)	Non-systematic Assessment	EG0002 affected42 at risk
muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE (4.0)	Non-systematic Assessment	EG0003 affected42 at risk
dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0004 affected42 at risk

Ancestor Terms

ID	Term
D002072	Butylene Glycols
D006018	Glycols
D000438	Alcohols
D009930	Organic Chemicals
D008698	Mesylates
D000476	Alkanesulfonates
D017738	Alkanesulfonic Acids
D000473	Alkanes
D006839	Hydrocarbons, Acyclic
D006838	Hydrocarbons
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D011034	Podophyllotoxin
D013764	Tetrahydronaphthalenes
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D011083	Polycyclic Compounds
D005960	Glucosides
D006027	Glycosides
D002241	Carbohydrates
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D013438	Sulfhydryl Compounds
D018380	Hematopoietic Stem Cell Transplantation
D033581	Stem Cell Transplantation
D017690	Cell Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D013812	Therapeutics
D013514	Surgical Procedures, Operative
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors
D018942	Macrolides
D007783	Lactones
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Term
D016403	Lymphoma, Large B-Cell, Diffuse
D008228	Lymphoma, Non-Hodgkin
D016399	Lymphoma, T-Cell
D020522	Lymphoma, Mantle-Cell
D006689	Hodgkin Disease
D015451	Leukemia, Lymphocytic, Chronic, B-Cell
D008223	Lymphoma

ID	Term
D016393	Lymphoma, B-Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D015448	Leukemia, B-Cell
D007945	Leukemia, Lymphoid
D007938	Leukemia
D006402	Hematologic Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D002066	Busulfan
D005047	Etoposide
D003520	Cyclophosphamide
D015080	Mesna
D036102	Peripheral Blood Stem Cell Transplantation
D000069585	Filgrastim
D016179	Granulocyte Colony-Stimulating Factor
C024352	fludarabine
C042382	fludarabine phosphate
D014180	Transplantation
D016559	Tacrolimus
D020123	Sirolimus
D008727	Methotrexate

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
respiratory failure	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected42 at risk
sepsis	Infections and infestations	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected42 at risk
Adult Respiratory Distress Syndrome	Respiratory, thoracic and mediastinal disorders	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected42 at risk
Atrioventricular block	Cardiac disorders	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected42 at risk
Death, not otherwise specified	General disorders	CTCAE (4.0)	Non-systematic Assessment	EG0001 affected42 at risk