Chemotherapy Followed by Allogeneic Stem Cell Transplantation for Hematologic Malignancies

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00741455
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arm: 1
• Duration (Months): 191
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine disease-free survival, overall survival, time to progression, regimen-related toxicity and/or treatment-related mortality in patients with hematologic malignancies treated with non-myeloablative chemotherapy followed by allogeneic stem cell transplant.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies	Procedure: Stem Cell Transplant; Drug: G-CSF; Drug: Fludarabine; Drug: cyclophosphamide; Drug: Cyclosporine; Drug: Methotrexate	N/A

Detailed Description

Allogeneic bone marrow transplantation (BMT) became feasible in the 1960s after elucidation of the Human Leukocyte Antigen (HLA) complex. Since then, the therapy has evolved into an effective treatment for many hematologic disorders. Otherwise incurable malignancies are frequently cured by this approach, with the likelihood of cure ranging from 10% to 85%, depending on the disease and the disease status. The treatment strategy incorporates very large doses of chemotherapy and often radiation to eliminate cancer cells and to immunosuppress the recipient to allow the engraftment of donor cells. Donor cells give rise to hematopoiesis within two to three weeks, rescuing the patient from the effects of high dose therapy. In the ideal situation, immune recovery and recipient-specific tolerance occurs over the following 6-18 months, and the patient is cured of their underlying malignancy, off immunosuppression, with a functionally intact donor-derived immune system. However, complications are common and include fatal organ damage from the effects of high dose chemotherapy, infection, hemorrhage, and, in particular, graft-versus-host disease (GvHD). A realistic estimate of transplant-related mortality in the standard HLA-matched sibling setting is approximately 25%. The risk of treatment-related mortality limits the success and certainly precludes its use in older patients. Thus, new strategies in transplantation are needed.

With the growing understanding that much of the curative potential of allogeneic bone marrow or stem cell transplant (SCT) is from an immune anti-tumor effect of donor cells, known as graft-versus-leukemia (GvL) or graft-versus-tumor (GvT), a new strategy is being employed that shifts the emphasis from high-dose chemo-radiotherapy to donor-derived, immune-mediated anti-tumor therapy. In this approach, patients receive preparative regimens that, while having some anti-tumor activity, are mainly designed to be immunosuppressive enough to allow engraftment of donor stem cells and lymphocytes. Engrafted lymphocytes then mediate a GvL effect; if the GvL effect of the initial transplant is not sufficient, then additional lymphocytes may be infused (achievement of engraftment allows additional lymphocytes to "take" in the recipient without requiring any additional conditioning of the recipient). The lower intensity of the preparative regimen lessens the overall toxicity by minimizing the doses of chemo-radiotherapy. In addition, less intensive preparative regimens may be associated with less GvHD, as much evidence suggests that high-dose therapy contributes to the syndrome of GvHD by causing tissue damage, leading to a cytokine milieu which enhances activation of graft-versus-host (GvH) effector cells. Thus, such an approach may allow the safer use of allogeneic transplants in standard populations and may allow extension of allogeneic transplantation to patients who could not receive standard (myeloablative) transplants because of age or co-morbidities. This protocol investigates a non-myeloablative transplant approach, using fludarabine and cyclophosphamide, to allow engraftment of allogeneic cells, which may then mediate anti-tumor effects.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-Myeloablative Chemotherapy Followed by HLA-Matched Related Allogeneic Stem Cell Transplantation for Hematologic Malignancies
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: May 1, 2020
• Actual Study Completion Date: May 1, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Study Treatment Chemotherapy, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate

Procedure: Stem Cell Transplant; Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml.; Other Names: HLA-Matched Related Allogeneic Stem Cell Transplantation ; Drug: G-CSF; 10 mcg/kg/day on days 5, 6, and 7; Drug: Fludarabine; 25 mg/m2/d IV over 30 minutes on days -6 to -2; Drug: cyclophosphamide; 1 g/m2/d IV on days -3 and -2; Drug: Cyclosporine; used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml; Drug: Methotrexate; used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Successful Bone Marrow Engraftment [Within 30 days of bone marrow transplant]

   Rates of successful engraftment.

Secondary Outcome Measures

1. Number of Participants Who Achieve Complete Donor Chimerism [Post-transplant days +30, +60, +100, +180 and +365]

   Complete donor chimerism

2. Number of Participants Who Experienced Graft-Versus-Host-Disease [Post-transplant procedure through death]

   Collect the number of incidents of acute and chronic graft-versus-host disease

3. Overall Survival Measured in Participants [Up to 15 Years Post-Transplant]

   Mortality rates in subjects after successful completion of a bone marrow transplant

4. Collection of Adverse Events [Until the 6th Bone Marrow Transplant performed in subjects on study]

   Determine the level of toxicity experienced by subjects who receive protocol treatment and bone marrow transplant

5. Assess Disease Response [Post-transplant procedure through death]

   Review and assess the tumor response rate

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age: 18-75 years

• Diseases

1. Chronic myelogenous leukemia (CML)

• First chronic phase or later

• Accelerated phase

1. Acute myelogenous or lymphoblastic leukemia (AML or ALL)

• Second or subsequent remission

• Patients who have failed an autologous PBSC transplant

• First remission with poor risk features, including, but not limited to: For AML- complex chromosome karyotype, abnormalities of chromosome 5 or 7, 12p-, 13+, 8+, t(9;22), t(11;23) For ALL- t(9;22), t(4;11), t(1;19), myeloid antigen coexpression

1. Myelodysplastic syndrome (MDS)

2. Multiple myeloma - high risk myeloma (poor responders, relapse after autologous PBSCT, chromosome 13 abnormalities)

3. Hodgkin's disease

• Primary refractory disease

• Relapsed disease (first relapse or later)

• Patients who have failed an autologous PBSC transplant

1. Non-Hodgkin's lymphoma Low grade (by Working Formulation)

• Relapsed, progressive disease after initial chemotherapy

• Primary refractory disease or failure to respond (>PR) to initial chemotherapy

• Patients who have failed an autologous PBSC transplant Intermediate grade (by Working Formulation)

• Relapsed disease

• Primary refractory disease or failure to respond (>PR) to initial chemo

• Mantle cell lymphoma

• Patients who have failed an autologous PBSC transplant

1. Chronic lymphocytic leukemia (CLL)

• Patients newly diagnosed with poor prognostic factors, including CD38 expression, Chromosome 11 or 17 abn

• T-CLL/PLL

• Relapsed or progressive disease, or refractory after Fludarabine

• Patients who have failed an autologous PBSC transplant

• Donor Availability: Six of six matched HLA A, B and DR identical sibling (or parent or child) or 5/6 related donor with single mismatch at Class I antigen (A or B)

• Karnofsky performance status of >70%

• Serum bilirubin <2x upper limit of normal; transaminases <3x normal (unless due to disease)

• 24 hr urine creatinine clearance of >40 ml/min.

• DLCO >50% predicted

• Left ventricular ejection fraction >35%

• No active infection

• Non-pregnant female

• Signed informed consent

• No major organ dysfunction or psychological problems that preclude compliance and completion of the clinical trial.

Exclusion Criteria

• Major organ dysfunction

• Pregnant or lactating female

• Active infection

• Psychological problems that preclude compliance and completion of the clinical trial

• Any other condition, that in the judgement of the investigator, affects participant safety or overall participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center

Investigators

• Principal Investigator: John M Hill, MD, Dartmouth-Hitchcock Medical Center
• Principal Investigator: Kenneth R Meehan, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 18, 2010

More Information

Publications

None provided.

• Responsible Party: John M. Hill, Jr., MD, Director, Allogeneic Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT00741455
• Other Study ID Numbers: D0345
• First Posted: Aug 26, 2008
• Last Update Posted: Nov 23, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by John M. Hill, Jr., MD, Director, Allogeneic Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center: Non-myeloablative transplant; Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Multiple Myeloma; Non-Hodgkin's Lymphoma; Myelodysplastic syndrome; Chronic Lymphocytic Leukemia; Hodgkin's Disease
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Cyclosporine; Cyclophosphamide; Methotrexate; Fludarabine; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Period Title: Overall Study
STARTED	18
COMPLETED	17
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Overall Participants	18
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	18 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57
Sex: Female, Male (Count of Participants)
Female	12 66.7%
Male	6 33.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Successful Bone Marrow Engraftment
Description	Rates of successful engraftment.
Time Frame	Within 30 days of bone marrow transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	17
Engrafted </= 15 Days	1 5.6%
Engrafted 16-30 Days	15 83.3%
Engrafted >30 Days	1 5.6%

2. Secondary Outcome

Title	Number of Participants Who Achieve Complete Donor Chimerism
Description	Complete donor chimerism
Time Frame	Post-transplant days +30, +60, +100, +180 and +365

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	17
Complete Chimerism 30 Days Post Transplant	2 11.1%
Complete Chimerism 60 Days Post Transplant	2 11.1%
Complete Chimerism 100 Days Post Transplant	3 16.7%
Complete Chimerism 180 Days Post Transplant	3 16.7%
Complete Chimerism 365 Days Post Transplant	4 22.2%
Chimerism Unknown	1 5.6%
Did not achieve complete donor chimerism	2 11.1%

3. Secondary Outcome

Title	Number of Participants Who Experienced Graft-Versus-Host-Disease
Description	Collect the number of incidents of acute and chronic graft-versus-host disease
Time Frame	Post-transplant procedure through death

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	0

4. Secondary Outcome

Title	Overall Survival Measured in Participants
Description	Mortality rates in subjects after successful completion of a bone marrow transplant
Time Frame	Up to 15 Years Post-Transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	17
Survival < 1 year post-transplant	2 11.1%
Survival 1 to < 5 years post-transplant	8 44.4%
Survival 5 to < 10 years post-transplant	0 0%
Survival 10+ years post-transplant	7 38.9%

5. Secondary Outcome

Title	Collection of Adverse Events
Description	Determine the level of toxicity experienced by subjects who receive protocol treatment and bone marrow transplant
Time Frame	Until the 6th Bone Marrow Transplant performed in subjects on study

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	0

6. Secondary Outcome

Title	Assess Disease Response
Description	Review and assess the tumor response rate
Time Frame	Post-transplant procedure through death

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure

Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
Measure Participants	0

Adverse Events

Time Frame	All-Cause Mortality was assessed for up to 15 years post-transplant. Adverse event data was not collected.
Adverse Event Reporting Description	Serious Adverse Event data was not collected. Other [Not Including Serious] Adverse Events were not monitored/assessed
Arm/Group Title	Study Treatment
Arm/Group Description	Chemo, stem cell transplantation, HLA-Matched related allogeneic stem cell transplantation, leukapheresis, G-CSF, peripheral blood stem cell transplant, fludarabine, cyclophosphamide, donor lymphocyte infusion, cyclosporine, methotrexate Stem Cell Transplant: Donor: Prior to mobilization, leukapheresis to collect CD3+ cells. The donor will then receive G-CSF (10 mcg/kg/day) with leukapheresis collection of peripheral blood stem cells on days 5, 6 and 7 as needed. Goal of leukapheresis will be > 5 x 106 CD34+cells/kg of recipient. Patient: Peripheral Blood Stem Cell (PBSC) Transplant. Fludarabine 25mg/m2/d IV over 30 minutes on days -6 to -2, followed by cyclophosphamide 1g/m2/d IV on days -3 and -2. This will be followed by allogeneic stem cell infusion 48 hours later. Donor Lymphocyte Infusion (DLI) and Adjustment of Immunosuppression: Cyclosporine (CSA) and methotrexate (MTX) will be used for GvHD prophylaxis with target CSA levels of 200-400 ng/ml. G-CSF: 10 mcg/k
All Cause Mortality
	Study Treatment
	Affected / at Risk (%)	# Events
Total	10/17 (58.8%)
Serious Adverse Events
	Study Treatment
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Study Treatment
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

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.