Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer

• Sponsor: Northside Hospital, Inc. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00827099
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Duration (Months): 41
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes	Biological: anti-thymocyte globulin; Drug: fludarabine phosphate; Drug: Melphalan; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: umbilical cord blood transplantation	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To evaluate the 100-day transplant-related (non-relapse) mortality in patients with hematologic malignancies undergoing reduced-intensity conditioning comprising fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.

Secondary

• To evaluate the 12-month transplant-related (non-relapse) mortality.

• To evaluate the days to neutrophil engraftment (ANC > 500/mm³).

• To evaluate the days to platelet engraftment (platelet count > 20,000/mm³ [unsupported]).

• To evaluate the risk of acute and chronic graft-vs-host disease.

• To evaluate percent donor chimerism contribution of each cord unit.

• To evaluate relapse rate.

• To evaluate disease-free and overall survival.

• To evaluate transfusion support needed for UCBT recipients.

OUTLINE:

• Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV over 4-6 hours on days -4 to -2.

• Transplantation: Patients undergo two sequential umbilical cord blood transplantations on day 0.

• Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously and then orally twice daily beginning on day -1 and continuing until day 60, followed by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally twice daily beginning on day 0 and continuing until day 30, followed by a taper until day 60 in the absence of GVHD.

After completion of study treatment, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Outcome Measures

Primary Outcome Measures

1. Number of Participants With 100 Day Transplant-related Mortality (TRM) [100 days]

   100 Day TRM is death within 100 days from transplant related complications

Secondary Outcome Measures

1. Number of Patients That Engrafted Blood Counts by 30 Days After Transplant [Day 30]

   Number of patients whose Absolute Neutrophil Count (ANC) recovered to >500 x10^3/uL for at least 3 consecutive days after transplant

2. Percentage of Donor and Host Chimerism of Each Cord Blood Unit [day 30, day 60, day 90]

   Evaluate the percentages of donor and host chimerism at multiple times post-transplant including Day 30, Day 60, Day 90 and monthly thereafter if the patient is not considered to have full chimerism.

3. Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant. [Day 30]

   Patients will be evaluated regularly for the development of graft versus host disease both acute & chronic.

4. Number of Patients Who Experience Disease Relapse Post-transplant [Day 100, 6 months, 1 year, 18 months, 24 months]

   Patients will have routine restaging to assess disease response at Day 100, 6 months, 1 year, 18 months and 24 months. If disease relapse is suspected, the patient will be evaluated at that time.

5. Number of Patients Who Survive Following Treatment on This Protocol [Through Death]

   Patients will be followed until death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell transplantation is deemed clinically appropriate, including any of the following:

• Chronic myelogenous leukemia, meeting one of the following criteria:

• In first chronic phase AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission by 3 months or major cytogenetic response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution or disease progression while on therapy

• In accelerated phase with < 15% blasts

• In blast crisis that has entered into a second chronic phase following induction chemotherapy

• Acute myelogenous leukemia, meeting one of the following criteria:

• In second or subsequent completion remission*

• Failed primary induction chemotherapy, but subsequently entered into a complete remission* with ≤ 2 subsequent re-induction chemotherapy treatment(s)

• In first complete remission* with poor-risk cytogenetics NOTE: *Complete remission is defined as < 5% blasts in bone marrow, no definitive evidence of disease by morphology, flow cytometry, or genetic studies, and no circulating blasts. Neutrophil and platelet count recovery will not be required.

• Acute lymphoblastic leukemia, meeting one of the following criteria:

• In second or subsequent complete remission

• In first complete remission AND t(9;22)

• Myelodysplastic syndromes, meeting the following criteria:

• High-risk disease, defined as International Prognostic Scoring System score of ≥ 1.5

• Less than 10% blasts at the time of study enrollment

• Chronic myelomonocytic leukemia

• Less than 10% blasts at the time of study enrollment

• Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the following criteria:

• Age < 55 years AND a Lille score of 1

• Lille score of 2

• Hemoglobin < 10 g/dL AND abnormal karyotype

• Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the following criteria:

• Rai stage I-IV disease

• Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous stem cell transplantation

• Chemosensitive or stable, non-bulky disease prior to transplant

• Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)

• Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma, follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting all of the following criteria:

• Failed ≥ 1 prior chemotherapy regimen or autologous stem cell transplantation

• Chemosensitive or stable, non-bulky disease prior to transplant

• Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens)

• Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the following criteria:

• Failed to achieve remission or recurred after either conventional chemotherapy or autologous stem cell transplantation

• Chemosensitive, non-bulky disease prior to transplant

• Hodgkin lymphoma, meeting all of the following criteria:

• Relapsed after prior autologous stem cell transplantation or after ≥ 2 combination chemotherapy regimens AND ineligible for autologous peripheral blood stem cell transplantation

• Chemosensitive, non-bulky disease prior to transplant

• Multiple myeloma, meeting one of the following criteria:

• Relapsed after autologous stem cell transplantation

• Relapsed after conventional therapies AND not a candidate for autologous stem cell transplantation

• No HLA-matched related or unrelated donor available

• Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and DRB1 with the patient and with each other (HLA C and DQ will not be used in the match strategy)

• Total combined nucleated cell dose from the 2 umbilical cord blood units must be

3.7 x 10^7 nucleated cells/kg (pre-freeze dose) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

• Karnofsky performance status 80-100%

• Adapted, weighted Charlson Comorbidity Index < 3

• Serum creatinine ≤ 2.0 mg/dL

• AST or ALT < 3 times upper limit of normal (ULN)

• Bilirubin < 1.5 times ULN

• Not pregnant or nursing

• LVEF ≥ 40%

• DLCO > 50%

• No hypoxia at rest with oxygen saturation < 92% on room air (corrected with bronchodilator therapy)

• No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection)

• No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate- to high-risk for developing severe hepatic disease

• No HIV infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342

Sponsors and Collaborators

• Northside Hospital, Inc.

Investigators

• Principal Investigator: Scott R. Solomon, MD, Blood and Marrow Transplant Group of Georgia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Northside Hospital, Inc.
• ClinicalTrials.gov Identifier: NCT00827099
• Other Study ID Numbers: CDR0000632453; BMTGG-NSH-801
• First Posted: Jan 22, 2009
• Last Update Posted: Mar 23, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by Northside Hospital, Inc.: accelerated phase cml; adult ALL in remission; adult AML in remission; adult AML with 11q23 (MLL) abnormalities; adult AML with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); blastic phase chronic myelogenous leukemia; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; prolymphocytic leukemia; recurrent adult T-cell leukemia/lymphoma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; cutaneous B-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult grade III lymphomatoid granulomatosis; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; chronic idiopathic myelofibrosis; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes
• Additional relevant MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome; Mycophenolic Acid; Fludarabine; Fludarabine phosphate; Melphalan; Tacrolimus; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Study was IRB approved on 6/8/06. The first patient was enrolled on 6/9/06. The last patient was enrolled on 12/22/08.
Pre-assignment Detail	There were no group assignments for this study. It was a single arm cord blood transplant study.

Arm/Group Title	Umbilical Cord Blood Transplantation
Arm/Group Description	Fludarabine 30 mg^m2 on days -7, -6, -5, -4 & -3 Melphalan 140 mg^m2 on day -2 Rabbit antithymocyte globulin (ATG) 6mg/kg divided over 3 days, Days -4,-3,-2. (Thymoglobulin 1.0mg/kg on day -4, and 2.5mg/kg/d on days -3, -2) Tacrolimus starting on day -1 as a continuous infusion of 0.03 mg/kg/d. Mycophenolate mofetil (MMF) IV 15mg/kg BID will start on Day 0
Period Title: Overall Study
STARTED	5
COMPLETED	5
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Umbilical Cord Blood Transplantation
Arm/Group Description	Fludarabine 30 mg^m2 on days -7, -6, -5, -4 & -3 Melphalan 140 mg^m2 on day -2 Rabbit antithymocyte globulin (ATG) 6mg/kg divided over 3 days, Days -4,-3,-2. (Thymoglobulin 1.0mg/kg on day -4, and 2.5mg/kg/d on days -3, -2) Tacrolimus starting on day -1 as a continuous infusion of 0.03 mg/kg/d. Mycophenolate mofetil (MMF) IV 15mg/kg BID will start on Day 0
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.8 (9.86)
Sex: Female, Male (Count of Participants)
Female	2 40%
Male	3 60%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With 100 Day Transplant-related Mortality (TRM)
Description	100 Day TRM is death within 100 days from transplant related complications
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	5
Number [participants]	0 0%

2. Secondary Outcome

Title	Number of Patients That Engrafted Blood Counts by 30 Days After Transplant
Description	Number of patients whose Absolute Neutrophil Count (ANC) recovered to >500 x10^3/uL for at least 3 consecutive days after transplant
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	5
Number [participants]	5 100%

3. Secondary Outcome

Title	Percentage of Donor and Host Chimerism of Each Cord Blood Unit
Description	Evaluate the percentages of donor and host chimerism at multiple times post-transplant including Day 30, Day 60, Day 90 and monthly thereafter if the patient is not considered to have full chimerism.
Time Frame	day 30, day 60, day 90

Outcome Measure Data

Analysis Population Description

This study was terminated early. No participants were analyzed.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	0

4. Secondary Outcome

Title	Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant.
Description	Patients will be evaluated regularly for the development of graft versus host disease both acute & chronic.
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

This study was terminated early. No participants were analyzed.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	0

5. Secondary Outcome

Title	Number of Patients Who Experience Disease Relapse Post-transplant
Description	Patients will have routine restaging to assess disease response at Day 100, 6 months, 1 year, 18 months and 24 months. If disease relapse is suspected, the patient will be evaluated at that time.
Time Frame	Day 100, 6 months, 1 year, 18 months, 24 months

Outcome Measure Data

Analysis Population Description

This study was terminated early. No participants were analyzed.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	0

6. Secondary Outcome

Title	Number of Patients Who Survive Following Treatment on This Protocol
Description	Patients will be followed until death
Time Frame	Through Death

Outcome Measure Data

Analysis Population Description

This study was terminated early. No participants were analyzed.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	High dose conditioning with Fludarabine & Melphalan
Measure Participants	0

Adverse Events

Arm/Group Title	Umbilical Cord Blood Transplantation
Arm/Group Description	Fludarabine 30 mg^m2 on days -7, -6, -5, -4 & -3 Melphalan 140 mg^m2 on day -2 Rabbit antithymocyte globulin (ATG) 6mg/kg divided over 3 days, Days -4,-3,-2. (Thymoglobulin 1.0mg/kg on day -4, and 2.5mg/kg/d on days -3, -2) Tacrolimus starting on day -1 as a continuous infusion of 0.03 mg/kg/d. Mycophenolate mofetil (MMF) IV 15mg/kg BID will start on Day 0
All Cause Mortality
	Umbilical Cord Blood Transplantation
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Umbilical Cord Blood Transplantation
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Umbilical Cord Blood Transplantation
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Decreased Hemoglobin	4/5 (80%)	4
Decreased Leukocytes (total WBC)	4/5 (80%)	4
Decreased Neutrophils/Granulocytes (ANC/AGC)	4/5 (80%)	4
Elevated AST	2/5 (40%)	2
Thrombocytopenia	3/5 (60%)	3
Cardiac disorders
Hypertension	3/5 (60%)	3
Pain - Cardiovascular (chest pain)	1/5 (20%)	1
Ventricular arrhythmia - tachycardia	1/5 (20%)	1
Eye disorders
Ocular/Visual - Itching eyes	1/5 (20%)	1
Ocular/Visual - tearing eyes	1/5 (20%)	1
Ocular/visual - dilated pupils	1/5 (20%)	1
Ocular/visual - stinging eyes	2/5 (40%)	2
Watery eye	1/5 (20%)	1
Gastrointestinal disorders
Anorexia	4/5 (80%)	4
Constipation	2/5 (40%)	2
Dehydration	1/5 (20%)	1
Diarrhea	5/5 (100%)	5
Esophagitis	1/5 (20%)	1
Gastrointestinal - abdominal tenderness	2/5 (40%)	2
Gastrointestinal - tickle in throat	1/5 (20%)	1
Gastrointestinal-other (early satiety)	1/5 (20%)	1
Heartburn/dyspepsia	2/5 (40%)	2
Hemorrhage - oral cavity	1/5 (20%)	1
Mucositis	4/5 (80%)	4
Nausea	5/5 (100%)	5
Pain - Gastrointestinal (throat pain)	2/5 (40%)	2
Vomiting	3/5 (60%)	3
General disorders
Constitutional Symptoms - weakness	2/5 (40%)	2
Fatigue	4/5 (80%)	4
Fever	5/5 (100%)	5
Pain - General (pain NOS)	3/5 (60%)	3
Pain - Neurology (headache)	5/5 (100%)	5
Rigors/chills	4/5 (80%)	4
Hepatobiliary disorders
Elevated ALT	2/5 (40%)	2
Infections and infestations
Infection - general bacteria	1/5 (20%)	1
Infection - BK virus	2/5 (40%)	2
Infection - CMV	3/5 (60%)	3
Infection - Clostridium Difficile	1/5 (20%)	1
Infection - HHV6	1/5 (20%)	1
Infection - MRSA	1/5 (20%)	1
Infection - MRSE	1/5 (20%)	1
Infection - corynebacterium	1/5 (20%)	1
Infection - enterococcus faecium	1/5 (20%)	1
Infection - pneumonia	1/5 (20%)	1
Infection - strep mitis	1/5 (20%)	1
Infection - strep viridans	1/5 (20%)	1
Infection - thrush	1/5 (20%)	1
Metabolism and nutrition disorders
Elevated ALK PHOS	1/5 (20%)	1
Elevated PTT	1/5 (20%)	1
Hyperbilirubinemia	1/5 (20%)	1
Hypercalcemia	1/5 (20%)	1
Hyperglycemia	4/5 (80%)	4
Hyperkalemia	2/5 (40%)	2
Hypermagnesemia	1/5 (20%)	1
Hypernatremia	1/5 (20%)	1
Hypoalbuminemia	4/5 (80%)	4
Hypocalcemia	4/5 (80%)	4
Hypokalemia	3/5 (60%)	3
Hypomagnesemia	5/5 (100%)	5
Hyponatremia	4/5 (80%)	4
Hypophosphatemia	2/5 (40%)	2
Musculoskeletal and connective tissue disorders
Edema	1/5 (20%)	1
Extremity - lower (unsteady gait)	1/5 (20%)	1
Lymphatics - spongiosis	1/5 (20%)	1
Musculoskeletal/Soft Tissue - Myalgia	1/5 (20%)	1
Musculoskeletal/soft tissue - aching in legs	1/5 (20%)	1
Musculoskeletal/soft tissue - arhthralgia	2/5 (40%)	2
Pain - musculoskeletal (back pain)	1/5 (20%)	1
Nervous system disorders
Cognitive Disturbance - unable to verbalize	2/5 (40%)	2
Cognitive disturbance - incomprehensible speech	2/5 (40%)	2
Confusion	2/5 (40%)	2
Extrapyramidal/involuntary movement/restlessness	1/5 (20%)	1
Memory impairment - short attention span	1/5 (20%)	1
Memory impairment - short term memory loss	1/5 (20%)	1
Mood alteration - aggitated/restless	3/5 (60%)	3
Mood alteration - anxiety	2/5 (40%)	2
Mood alteration - depression	2/5 (40%)	2
Mood alteration - flat affect	1/5 (20%)	1
Mood alteration - tearful	2/5 (40%)	2
Mood alteration - withdrawn	1/5 (20%)	1
Neuropathy - sensory (peripheral neuropathy)	1/5 (20%)	1
Seizure	1/5 (20%)	1
Tremor	1/5 (20%)	1
Psychiatric disorders
Insomnia	1/5 (20%)	1
Neurology (hallucinations)	1/5 (20%)	1
Renal and urinary disorders
Elevated creatinine	1/5 (20%)	1
Hemorrhage - GU (hemorrhagic cystitis)	1/5 (20%)	1
Renal/Genitourinary - difficulty urinating	1/5 (20%)	1
Renal/Genitourinary - dysuria	3/5 (60%)	3
Renal/Genitourinary - prostate enlargement	1/5 (20%)	1
Renal/Genitourinary - sphincter spasms	1/5 (20%)	1
Renal/Genitourinary - urinary hesitancy	1/5 (20%)	1
Urinary frequency/urgency	2/5 (40%)	2
Urinary retention	2/5 (40%)	2
Reproductive system and breast disorders
Hemorrhage - GU (vaginal bleeding)	1/5 (20%)	1
Pain - sexual/reproductive function (vaginal pain)	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/5 (40%)	2
Dyspnea	2/5 (40%)	2
Hiccoughs	2/5 (40%)	2
Hypotension	2/5 (40%)	2
Hypoxia	1/5 (20%)	1
Pulmonary/Upper Respiratory - Respiratory Failure	1/5 (20%)	1
Pulmonary/Upper Respiratory - sinus congestion	1/5 (20%)	1
Skin and subcutaneous tissue disorders
Dermatology/Skin - Nail slough	1/5 (20%)	1
Dermatology/Skin - nail burning	1/5 (20%)	1
Dermatology/Skin - skin sensitivity	2/5 (40%)	2
Dermatology/skin - "cut on skin"	1/5 (20%)	1
Dermatology/skin - clubbing of fingernails	2/5 (40%)	2
Dermatology/skin - discoloration of fingernails	1/5 (20%)	1
Dermatology/skin - irritation	2/5 (40%)	2
Dermatology/skin- burning palms	1/5 (20%)	1
Dry skin	1/5 (20%)	1
Flushing	2/5 (40%)	2
Pruritis/itching	4/5 (80%)	4
Rash	4/5 (80%)	4

Limitations/Caveats

This study was terminated early, therefore no additional data measures or outcomes are available.

More Information

Certain Agreements

Principal Investigators are NOT 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.