RISE: Rabbit Anti-thymocyte Globulin in the Treatment of Patients With Low to Intermediate-1 Risk Myelodysplastic Syndrome

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00542828
• Collaborator: (none)
• Enrollment: 16
• Locations: 7
• Arm: 1
• Duration (Months): 21
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase II, single-arm, open-label, multinational, multicenter study of rATG in patients with low or intermediate-1 risk MDS who have either failed 1 prior treatment with growth factor(s), hypomethylating agents (5-azacitidine or decitabine), or the antiangiogenic agents lenalidomide or thalidomide, or who have never been treated for MDS (i.e., treatment-naïve patients).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome (MDS)	Biological: Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of the Efficacy of Rabbit Anti-thymocyte Globulin (rATG) in Patients With Low and Intermediate-1 Risk Myelodysplastic Syndrome
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Thymoglobulin	Biological: Thymoglobulin®, Rabbit Anti-thymocyte Globulin (rATG); All patients were to be treated with rATG 3.75 mg/kg/day administered by intravenous (IV) infusion over ≥6 hours for 5 consecutive days (cumulative dose: 18.75 mg/kg); Other Names: Rabbbit Anti-human thymocyte immunoglobulin

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Achieved Hematologic Improvement (HI) [12 months]

   This is a measure of HI in the erythroid, platelet, and neutrophil lineages. Note that HI was observed in the erythroid lineage only, which is defined as a participant who had a >=1.5 g/dL increase in hemoglobin from baseline (pretreatment value must have been <11 g/dL) and who had a relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of >=4 RBC transfusions over 8 weeks as compared with the pretreatment transfusion number in the previous 8 weeks. These criteria were taken from the 2006 International Working Group criteria.

Secondary Outcome Measures

1. Number of Participants With Duration of HI [36 months]

   This is a measure of the duration of HI for those participants who achieved HI. Duration of HI is defined as the time from confirmation of HI response to the date of first documentation of HI relapse or death due to any cause, whichever occurs first.

2. Number of Participants Who Achieved Disease Remission [36 months]

   Disease remission is defined as a participant whose best response to therapy was a complete remission or partial remission. A complete remission is defined as: bone marrow <=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia noted; and peripheral blood hemoglobin >=11 g/dL, platelets >=100 x 10^9/L, neutrophils >=1.0 x 10^9/L, and blasts 0%. Partial remission is defined as: all complete remission criteria if abnormal before treatment, except bone marrow blasts decreased by >=50% over pretreatment, but still >5%; and cellularity and morphology not relevant.

3. Duration of Disease Remission [36 months]

   This is a measure of the duration of overall disease remission only for those participants who achieved an overall remission. Duration of overall remission is defined as the time from first documentation of overall remission to the date of first documentation of disease relapse or death due to any cause, whichever occurs first.

4. Number of Participants Who Achieved Transfusion Independence [36 months]

   This is a measure of transfusion independence, which is defined as a participant with no transfusions for a period of 8 consecutive calendar weeks after first dose. Transfusion independence was to be calculated only for those participants who had documented transfusions during the 8 weeks prior to enrollment.

5. Number of Participants With Duration of Transfusion Independence [36 months]

   This is a measure of the duration of transfusion independence only for those participants who achieved transfusion independence. Duration of transfusion independence is defined as the longest period of time during which a participant requires no transfusions.

6. Number of Participants With a Relapse Following HI [36 months]

   This is a measure of relapse following HI, which is defined as a participant who experiences at least one of the following: >=50% decrease from maximum response levels in granulocytes or platelets; >=1.5 g/dL reduction in hemoglobin; or transfusion dependence.

7. Number of Participants With a Relapse Following Overall Remission [36 months]

   This is a measure of relapse following an overall remission only for participants who experienced either a complete or partial remission. Relapse following an overall remission is defined as a participant who meets any of the following criteria: a return to pretreatment bone marrow blast percentage; decrease of >=50% from maximum remission levels in neutrophils or platelets; reduction in hemoglobin concentration by >=1.5 g/dL from maximum remission levels; or transfusion dependence.

8. Number of Participants With Progression-free Survival [36 months]

   This is a measure of a progression-free survival which is defined as the time from the participant's first dose to the date of disease progression, lost to follow-up or death due to any cause, whichever occurs first.

9. Number of Participants With Transformation to Acute Myeloid Leukemia [36 months]

   This is a measure of transformation to acute myeloid leukemia only for participants who have bone marrow assessments. Transformation to acute myeloid leukemia is defined as the earliest date a participant experiences bone marrow blasts of >=20% after the start of treatment.

10. Number of Participants With a Cytogenetic Response [36 months]

    This is a measure of cytogenic response for participants whose best response to therapy is a either a complete or partial cytogenetic response. A complete cytogenetic response is defined as the disappearance of the chromosomal abnormality without appearance of new ones. A partial cytogenetic response is defined as at least 50% reduction of the chromosomal abnormality.

11. Number of Participants With a Marrow Remission [36 months]

    This is a measure of bone marrow complete remission for participants who experience a remission. Bone marrow complete remission is defined as a bone marrow assessment of <=5% myeloblasts and decrease by >=50% over pretreatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient provided signed written informed consent.

• Patient had pathologically confirmed low or intermediate-1 risk MDS at the time of MDS diagnosis and at the time of screening.

• Patient had received no more than 1 prior treatment for MDS.

• Patient exhibited at least 1 hematologic cytopenia (anemia, neutropenia, or thrombocytopenia) over a period of ≥1 week.

• Patient had documentation of any prior transfusion requirements.

• Patient had an Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or

• Patient was ≥18 and ≤70 years of age at time of signing the informed consent document (ICD).

• Patient was able to adhere to study visit schedule and all other protocol requirements.

• Patient was willing to practice a medically approved method of birth control during participation in the study (at least 12 months after the last infusion of rATG) (fertile male and female patients).

Exclusion Criteria:

• Patient was pregnant or lactating.

• Patient has had prior treatment with any ATG.

• Patient has received any immunomodulatory or immunosuppressing agents (excluding steroids) <12 weeks prior to the first infusion of rATG.

• Patient has had a prior hematopoietic stem cell transplantation and/or other organ transplant.

• Patient has had a prior allergic reaction to rabbit proteins or excipients.

• Patient had any of the following subtypes of MDS: refractory anemia with ringed sideroblasts (RARS); chronic myelomonocytic leukemia (CMML) if white blood counts

13x10^9/L; or other MDS/myeloproliferative diseases (MPD).

• Patient had MDS associated with a 5q chromosomal deletion unless the patient received prior lenalidomide treatment <4 weeks prior to the first infusion of rATG.

• Patient had MDS presumed secondary to exposure to chemicals or treatment with radiotherapy or chemotherapy.

• Patient received any investigational agents within 4 weeks prior to the first infusion of rATG.

• Patient has any of the following abnormalities: serum creatinine >1.5 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) >2.5 x ULN; or serum total bilirubin >1.5 x ULN, except for unconjugated hyperbilirubinemia related to the patient's MDS.

• Patient received any treatment with non-steroidal anti-inflammatory drugs (NSAIDs) within 14 days prior to the start of treatment.

• Patient was known to be human immunodeficiency virus (HIV) positive.

• Patient had any prior diagnosis of malignancy other than MDS, unless the patient had been disease-free for at least 5 years following the completion of curative intent therapy.

• Patient had any serious medical condition (other than MDS) that would limit survival to <2 years.

• Patient had active acute or chronic infection, including cytomegaloviremia (CMV) infection or deep tissue infection.

• Patient had any other serious medical condition, uncontrolled illness (including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia), social condition, or psychiatric illness that would prevent the patient from signing the informed consent document (ICD), or would place the patient at unacceptable risk if he/she participated in the study, or that would limit compliance with study requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hopital Avicenne/University	Paris		France	93009
2	St. Johannes-Hospital Duisburg	Duisburg		Germany	47166
3	Medizinische Hochschule Hannover	Hannover		Germany	30625
4	UMC St Radboud Centraal	Nijmegen		Netherlands	6525 GA
5	Royal Bournemouth Hospital	Bournemouth	England	United Kingdom	BH7 7DW
6	St. James Hospital	Leeds	England	United Kingdom	LS9 7TF
7	King's College Hospital	London	England	United Kingdom	SE5 9RS

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00542828
• Other Study ID Numbers: ThymoHEM01206; 2007-002532-28
• First Posted: Oct 12, 2007
• Last Update Posted: Apr 3, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Immunoglobulins; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Enrollment period: 05 November 2007 through 06 May 2009. Study participants were enrolled at 7 study centers in Europe.
Pre-assignment Detail	Because the study was terminated early due to slow enrollment, only 16 participants were enrolled in the study. Of these, 14 participants went on to receive treatment with Thymoglobulin.

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Period Title: Overall Study
STARTED	16
COMPLETED	3
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Overall Participants	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.4 (7.67)
Age, Customized (participants) [Number]
<60 years	10 71.4%
>=60 years	4 28.6%
Sex: Female, Male (Count of Participants)
Female	7 50%
Male	7 50%
Race/Ethnicity, Customized (participants) [Number]
Black	1 7.1%
White	11 78.6%
Not Reported	2 14.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Achieved Hematologic Improvement (HI)
Description	This is a measure of HI in the erythroid, platelet, and neutrophil lineages. Note that HI was observed in the erythroid lineage only, which is defined as a participant who had a >=1.5 g/dL increase in hemoglobin from baseline (pretreatment value must have been <11 g/dL) and who had a relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of >=4 RBC transfusions over 8 weeks as compared with the pretreatment transfusion number in the previous 8 weeks. These criteria were taken from the 2006 International Working Group criteria.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Number of participants analyzed includes those who received treatment with Thymoglobulin and completed follow-up efficacy assessments. However, no formal efficacy analysis was conducted due to the small sample size and early study termination.

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	13
Number [participants]	3 21.4%

2. Secondary Outcome

Title	Number of Participants With Duration of HI
Description	This is a measure of the duration of HI for those participants who achieved HI. Duration of HI is defined as the time from confirmation of HI response to the date of first documentation of HI relapse or death due to any cause, whichever occurs first.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

3. Secondary Outcome

Title	Number of Participants Who Achieved Disease Remission
Description	Disease remission is defined as a participant whose best response to therapy was a complete remission or partial remission. A complete remission is defined as: bone marrow <=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia noted; and peripheral blood hemoglobin >=11 g/dL, platelets >=100 x 10^9/L, neutrophils >=1.0 x 10^9/L, and blasts 0%. Partial remission is defined as: all complete remission criteria if abnormal before treatment, except bone marrow blasts decreased by >=50% over pretreatment, but still >5%; and cellularity and morphology not relevant.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

4. Secondary Outcome

Title	Duration of Disease Remission
Description	This is a measure of the duration of overall disease remission only for those participants who achieved an overall remission. Duration of overall remission is defined as the time from first documentation of overall remission to the date of first documentation of disease relapse or death due to any cause, whichever occurs first.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

5. Secondary Outcome

Title	Number of Participants Who Achieved Transfusion Independence
Description	This is a measure of transfusion independence, which is defined as a participant with no transfusions for a period of 8 consecutive calendar weeks after first dose. Transfusion independence was to be calculated only for those participants who had documented transfusions during the 8 weeks prior to enrollment.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

6. Secondary Outcome

Title	Number of Participants With Duration of Transfusion Independence
Description	This is a measure of the duration of transfusion independence only for those participants who achieved transfusion independence. Duration of transfusion independence is defined as the longest period of time during which a participant requires no transfusions.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants With a Relapse Following HI
Description	This is a measure of relapse following HI, which is defined as a participant who experiences at least one of the following: >=50% decrease from maximum response levels in granulocytes or platelets; >=1.5 g/dL reduction in hemoglobin; or transfusion dependence.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

8. Secondary Outcome

Title	Number of Participants With a Relapse Following Overall Remission
Description	This is a measure of relapse following an overall remission only for participants who experienced either a complete or partial remission. Relapse following an overall remission is defined as a participant who meets any of the following criteria: a return to pretreatment bone marrow blast percentage; decrease of >=50% from maximum remission levels in neutrophils or platelets; reduction in hemoglobin concentration by >=1.5 g/dL from maximum remission levels; or transfusion dependence.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

Secondary outcome measure was not formally analyzed or assessed due to early study termination and small sample size (i.e., no study participants reached the 36-month time point)

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

9. Secondary Outcome

Title	Number of Participants With Progression-free Survival
Description	This is a measure of a progression-free survival which is defined as the time from the participant's first dose to the date of disease progression, lost to follow-up or death due to any cause, whichever occurs first.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

10. Secondary Outcome

Title	Number of Participants With Transformation to Acute Myeloid Leukemia
Description	This is a measure of transformation to acute myeloid leukemia only for participants who have bone marrow assessments. Transformation to acute myeloid leukemia is defined as the earliest date a participant experiences bone marrow blasts of >=20% after the start of treatment.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

11. Secondary Outcome

Title	Number of Participants With a Cytogenetic Response
Description	This is a measure of cytogenic response for participants whose best response to therapy is a either a complete or partial cytogenetic response. A complete cytogenetic response is defined as the disappearance of the chromosomal abnormality without appearance of new ones. A partial cytogenetic response is defined as at least 50% reduction of the chromosomal abnormality.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

12. Secondary Outcome

Title	Number of Participants With a Marrow Remission
Description	This is a measure of bone marrow complete remission for participants who experience a remission. Bone marrow complete remission is defined as a bone marrow assessment of <=5% myeloblasts and decrease by >=50% over pretreatment.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

This secondary outcome measure was not formally analyzed or assessed due to the small sample size and early study termination (i.e., no study participants reached the 36-month time point).

Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
Measure Participants	0

Adverse Events

Time Frame	Adverse events were collected for approximately 19 months (includes all events which presented after the start of treatment through the end of study).
Adverse Event Reporting Description	In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Arm/Group Title	Thymoglobulin
Arm/Group Description	Thymoglobulin 3.75 mg/kg/day for 5 consecutive days
All Cause Mortality
	Thymoglobulin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Thymoglobulin
	Affected / at Risk (%)	# Events
Total	7/14 (50%)
Cardiac disorders
Bradycardia	1/14 (7.1%)
Gastrointestinal disorders
Constipation	1/14 (7.1%)
Intestinal perforation	1/14 (7.1%)
Rectal haemorrhage	2/14 (14.3%)
General disorders
Oedema peripheral	1/14 (7.1%)
Pyrexia	1/14 (7.1%)
Immune system disorders
Serum sickness	2/14 (14.3%)
Infections and infestations
Cellulitis	1/14 (7.1%)
Influenza	1/14 (7.1%)
Sepsis	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Myalgia	1/14 (7.1%)
Myositis	1/14 (7.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	1/14 (7.1%)
Renal and urinary disorders
Renal failure acute	1/14 (7.1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/14 (7.1%)
Other (Not Including Serious) Adverse Events
	Thymoglobulin
	Affected / at Risk (%)	# Events
Total	14/14 (100%)
Blood and lymphatic system disorders
Anaemia	2/14 (14.3%)
Febrile neutropenia	1/14 (7.1%)
Neutropenia	2/14 (14.3%)
Pancytopenia	1/14 (7.1%)
Thrombocytopenia	2/14 (14.3%)
Cardiac disorders
Arrhythmia	1/14 (7.1%)
Tachycardia	1/14 (7.1%)
Ear and labyrinth disorders
Deafness	1/14 (7.1%)
Eye disorders
Conjunctival haemorrhage	1/14 (7.1%)
Eye pain	1/14 (7.1%)
Scleral hyperaemia	1/14 (7.1%)
Visual impairment	1/14 (7.1%)
Gastrointestinal disorders
Abdominal distension	1/14 (7.1%)
Abdominal pain	2/14 (14.3%)
Abdominal tenderness	1/14 (7.1%)
Diarrhoea	10/14 (71.4%)
Dry mouth	3/14 (21.4%)
Dysphagia	1/14 (7.1%)
Haemorrhoidal haemorrhage	1/14 (7.1%)
Mouth haemorrhage	1/14 (7.1%)
Mouth ulceration	1/14 (7.1%)
Nausea	5/14 (35.7%)
Oral pain	1/14 (7.1%)
Rectal haemorrhage	1/14 (7.1%)
Toothache	1/14 (7.1%)
Vomiting	4/14 (28.6%)
General disorders
Catheter site pain	1/14 (7.1%)
Chills	3/14 (21.4%)
Fatigue	3/14 (21.4%)
Injection site reaction	1/14 (7.1%)
Local swelling	1/14 (7.1%)
Non-cardiac chest pain	1/14 (7.1%)
Oedema	1/14 (7.1%)
Oedema peripheral	3/14 (21.4%)
Pyrexia	9/14 (64.3%)
Immune system disorders
Cytokine release syndrome	1/14 (7.1%)
Serum sickness	3/14 (21.4%)
Infections and infestations
Central line infection	1/14 (7.1%)
Epstein-Barr virus infection	1/14 (7.1%)
Folliculitis	1/14 (7.1%)
Gastroenteritis	1/14 (7.1%)
Lower respiratory tract infection	1/14 (7.1%)
Nasopharyngitis	2/14 (14.3%)
Staphylococcal infection	1/14 (7.1%)
Upper respiratory tract infection	1/14 (7.1%)
Injury, poisoning and procedural complications
Transfusion reaction	1/14 (7.1%)
Investigations
Blood glucose increased	1/14 (7.1%)
Blood lactate dehydrogenase increased	1/14 (7.1%)
Blood phosphorus decreased	1/14 (7.1%)
Blood potassium decreased	1/14 (7.1%)
Blood sodium increased	1/14 (7.1%)
Blood urine present	1/14 (7.1%)
Hepatic enzyme increased	1/14 (7.1%)
Liver function test abnormal	1/14 (7.1%)
Neutrophil count decreased	1/14 (7.1%)
Platelet count decreased	2/14 (14.3%)
Protein urine present	1/14 (7.1%)
Weight increased	2/14 (14.3%)
Metabolism and nutrition disorders
Anorexia	1/14 (7.1%)
Decreased appetite	1/14 (7.1%)
Hyperglycaemia	3/14 (21.4%)
Hypocalcaemia	1/14 (7.1%)
Hypokalaemia	4/14 (28.6%)
Hypomagnesaemia	1/14 (7.1%)
Hypophosphataemia	1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/14 (35.7%)
Arthritis	1/14 (7.1%)
Back pain	1/14 (7.1%)
Bone pain	1/14 (7.1%)
Flank pain	1/14 (7.1%)
Muscle spasms	1/14 (7.1%)
Musculoskeletal chest pain	1/14 (7.1%)
Musculoskeletal pain	1/14 (7.1%)
Myalgia	1/14 (7.1%)
Neck pain	1/14 (7.1%)
Pain in extremity	3/14 (21.4%)
Pain in jaw	1/14 (7.1%)
Nervous system disorders
Benign intracranial hypertension	1/14 (7.1%)
Dizziness	1/14 (7.1%)
Dysgeusia	1/14 (7.1%)
Headache	6/14 (42.9%)
Lethargy	3/14 (21.4%)
Paraesthesia	2/14 (14.3%)
Syncope	1/14 (7.1%)
Tremor	1/14 (7.1%)
Psychiatric disorders
Insomnia	1/14 (7.1%)
Reproductive system and breast disorders
Genital ulceration	1/14 (7.1%)
Menorrhagia	1/14 (7.1%)
Menstrual disorder	1/14 (7.1%)
Sexual dysfunction	1/14 (7.1%)
Vaginal haemorrhage	2/14 (14.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/14 (7.1%)
Dyspnoea	1/14 (7.1%)
Dyspnoea exertional	1/14 (7.1%)
Epistaxis	4/14 (28.6%)
Hypoxia	1/14 (7.1%)
Oropharyngeal pain	3/14 (21.4%)
Skin and subcutaneous tissue disorders
Alopecia	2/14 (14.3%)
Dermatitis allergic	1/14 (7.1%)
Dry skin	2/14 (14.3%)
Ecchymosis	1/14 (7.1%)
Eczema	2/14 (14.3%)
Erythema	1/14 (7.1%)
Hyperhidrosis	1/14 (7.1%)
Pain of skin	1/14 (7.1%)
Petechiae	2/14 (14.3%)
Pruritus	2/14 (14.3%)
Pruritus generalised	1/14 (7.1%)
Purpura	1/14 (7.1%)
Rash	5/14 (35.7%)
Rash erythematous	2/14 (14.3%)
Rash macular	2/14 (14.3%)
Rash maculo-papular	1/14 (7.1%)
Rash pruritic	1/14 (7.1%)
Skin chapped	1/14 (7.1%)
Skin exfoliation	1/14 (7.1%)
Skin lesion	1/14 (7.1%)
Stasis dermatitis	1/14 (7.1%)
Swelling face	1/14 (7.1%)
Vascular disorders
Cardiovascular insufficiency	1/14 (7.1%)
Flushing	2/14 (14.3%)
Hypertension	3/14 (21.4%)
Hypotension	4/14 (28.6%)

Limitations/Caveats

The study was terminated early due to a slow enrollment rate; therefore, only safety data were collected from participants for 45 days following the last day of infusion (Day 5).

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.