Nonmyeloablative Conditioning and Transplantation for Patients With Refractory Systemic Lupus Erythematosus (SLE)

• ClinicalTrials.gov Identifier: NCT02080195
• Recruitment Status: Terminated
• First Posted: March 6, 2014
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2019
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Maryland Stem Cell Research Fund
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Lupus Erythematosus; Graft-versus-host Disease
• Interventions: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Rabbit antithymocyte globulin; Radiation: Total body irradiation; Biological: Allogeneic bone marrow transplant
• Enrollment: 1

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Period Title: Overall Study
Started	1
Completed	1
Not Completed	0

Baseline Characteristics

Arm/Group Title		Nonmyeloablative Conditioning and BMT
Arm/Group Description		Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Baseline Participants		1
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	1 100.0%
	>=65 years	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Female	1 100.0%
	Male	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	1 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	1 100.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants
		1

Outcome Measures

1. Primary Outcome

Title	The Feasibility of the Conditioning Regimen and Post Transplantation Cyclophosphamide in Refractory SLE Patients With Donors Having Various Degrees of Matching
Description	Number of participants who were alive at 1 year after transplant and who had not suffered graft rejection, acute or chronic GVHD, or Grade 3 or higher (CTCAE V4.0) adverse events.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
	1 100.0%

2. Secondary Outcome

Title	RIFLE Score
Description	Change in Responder Index for Systemic Lupus Erythematosis (RIFLE) assessment. This is a qualitative assessment of organ function. The 12 month response will be assessed as: complete= complete or partial resolution in more than one organ, partial= complete or partial resolution in at least one organ, the same= no change or no worsening in any organ, worse= worsening in any organ
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The only enrolled participant on this study was never assessed for a follow-up RIFLE scale, so no data was collected for this outcome measure.

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3. Secondary Outcome

Title	Survival
Description	Number of patients alive and alive without relapse, respectively.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
Overall Survival	1 100.0%
Event Free Survival	1 100.0%

4. Secondary Outcome

Title	Graft Failure
Description	Number of participants with primary and/or secondary graft failure.
Time Frame	60 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
Primary graft failure	0 0.0%
Secondary graft failure	0 0.0%

5. Secondary Outcome

Title	Acute Graft Versus Host Disease (GVHD)
Description	Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
Grades II-IV acute GVHD	0 0.0%
Grades III-IV acute GVHD	0 0.0%

6. Secondary Outcome

Title	Chronic Graft Versus Host Disease (GVHD)
Description	Percentage of participants who developed chronic GVHD as defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Mild chronic GVHD involves only 1 or 2 organs or sites (except the lung), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites). Moderate chronic GVHD involves 1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR 2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site).
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description:	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
Overall Number of Participants Analyzed	1
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

Adverse Events

Time Frame	Adverse events were assessed weekly through at least Day 60.
Adverse Event Reporting Description	Reportable serious adverse events per protocol include: any mortality within the first 100 days after bone marrow transplant (BMT), any graft failures (defined as <5% donor chimerism) associated with failure of neutrophil recovery to >500/mm³ by day ~60 after transplantation, and all unexpected events as deemed significant by the PIs. Other events were neither tracked nor reported for this study.
Arm/Group Title	Nonmyeloablative Conditioning and BMT
Arm/Group Description	Nonmyeloablative Conditioning and Bone Marrow Transplant in Systemic Lupus Erythematosus patients Cyclophosphamide: Cyclophosphamide (alkylating agent) conditioning regimen and post transplantation cyclophosphamide with matched, partially matched, haplo-identical or unrelated donors Sodium-2-mercapto ethane sulphonate: Antineoplastic detoxifying agent Fludarabine monophosphate: Purine antimetabolite Tacrolimus: Calcineurin inhibitor Mofetil: Immunosuppressant Rabbit antithymocyte globulin: Selective immunosuppressant
All-Cause Mortality
	Nonmyeloablative Conditioning and BMT
	Affected / at Risk (%)
Total	0/1 (0.00%)
Serious Adverse Events
	Nonmyeloablative Conditioning and BMT
	Affected / at Risk (%)
Total	0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Nonmyeloablative Conditioning and BMT
	Affected / at Risk (%)
Total	0/1 (0.00%)

Limitations and Caveats

[Not Specified]

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.

Results Point of Contact

• Name/Title: Javier Bolaños Meade, MD
• Organization: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Phone: 410-614-6398
• EMail: fbolano2@jhmi.edu

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT02080195
• Other Study ID Numbers: J13134; NA_00082453 ( Other Identifier: Johns Hopkins IRB )
• First Submitted: February 28, 2014
• First Posted: March 6, 2014
• Results First Submitted: September 6, 2018
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2019