Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

• ClinicalTrials.gov Identifier: NCT00134017
• Recruitment Status: Completed
• First Posted: August 24, 2005
• Results First Posted: August 31, 2018
• Last Update Posted: August 31, 2018
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: National Cancer Institute (NCI)
• 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: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes
• Interventions: Drug: Busulfan; Drug: Cyclophosphamide
• Enrollment: 142

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Period Title: Overall Study
Started	142
Completed	142
Not Completed	0

Baseline Characteristics

Arm/Group Title		Bone Marrow Transplant
Arm/Group Description		Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Baseline Participants		142
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	142 participants
	<=18 years	16 11.3%
	Between 18 and 65 years	123 86.6%
	>=65 years	3 2.1%
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	142 participants
		47; (21 to 66)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	142 participants
	Female	66 46.5%
	Male	76 53.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Develop 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	Day 100

Outcome Measure Data

Analysis Population Description

The study data was analyzed early after 117 participants had been treated. This was done in order to publish the data and establish a new local standard of care at our institution. GVHD data was collected on 15 additional participants for a total of 132. GVHD data was not collected on the remaining 10 participants.

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description:	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Participants Analyzed	132
Measure Type: Count of Participants; Unit of Measure: Participants
Grades II-IV acute GVHD	49 37.1%
Grades III-IV acute GVHD	10 7.6%

2. Secondary Outcome

Title	Days to Engraftment
Description	Median number of days to neutrophil and platelet engraftment.
Time Frame	Up to one year

Outcome Measure Data

Analysis Population Description

The study data was analyzed early after 117 participants had been treated. This was done in order to publish the data and establish a new local standard of care at our institution. Engraftment data was not collected on the remaining 25 participants. Recipients of related-donor (n=78) and unrelated-donor (n=39) transplants were reported separately.

Arm/Group Title		Bone Marrow Transplant
Arm/Group Description:		Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Participants Analyzed		117
Median (Full Range); Unit of Measure: days
Neutrophil engraftment, related donors	Number Analyzed	78 participants
		23; (2 to 100)
Neutrophil engraftment, unrelated donors	Number Analyzed	39 participants
		25; (2 to 100)
Platelet engraftment, related donors	Number Analyzed	78 participants
		31; (5 to 354)
Platelet engraftment, unrelated donors	Number Analyzed	39 participants
		35; (5 to 354)

3. Secondary Outcome

Title	Chimerism
Description	Number of patients who achieved 100% donor chimerism.
Time Frame	Day 30, Day 60

Outcome Measure Data

Analysis Population Description

The study data was analyzed early after 117 participants had been treated. This was done in order to publish the data and establish a new local standard of care at our institution. Chimerism data was not collected on the remaining 25 participants. One participant died prior to Day 30 and was not analyzed for this outcome.

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description:	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Participants Analyzed	116
Measure Type: Count of Participants; Unit of Measure: Participants
Day 30	99 85.3%
Day 60	101 87.1%

4. Secondary Outcome

Title	Non-relapse Mortality
Description	Percentage of participants who died for BMT-related reasons.
Time Frame	Day 100, 2 years

Outcome Measure Data

Analysis Population Description

The study data was analyzed early after 117 participants had been treated. This was done in order to publish the data and establish a new local standard of care at our institution. NRM data was not collected on the remaining 25 participants.

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description:	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Participants Analyzed	117
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
Day 100	6; (2 to 13)
2 years	15; (8 to 24)

5. Secondary Outcome

Title	Relapse
Description	Percentage of participants who developed relapse or progressive disease.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

The study data was analyzed early after 117 participants had been treated. This was done in order to publish the data and establish a new local standard of care at our institution. Relapse data was not collected on the remaining 25 participants.

Arm/Group Title	Bone Marrow Transplant
Arm/Group Description:	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis.
Overall Number of Participants Analyzed	117
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	44; (34 to 53)

Adverse Events

Time Frame	Up to one year
Adverse Event Reporting Description	Adverse events were tracked systematically for 30-60 days depending on exact discharge date from the initial hospitalization. Only the following adverse events were collected: all graft failures; deaths in the first sixty days; unexpected grade 4-5 events.
Arm/Group Title	Bone Marrow Transplant
Arm/Group Description	Myeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis
All-Cause Mortality
	Bone Marrow Transplant
	Affected / at Risk (%)
Total	66/142 (46.48%)
Serious Adverse Events
	Bone Marrow Transplant
	Affected / at Risk (%)	# Events
Total	20/142 (14.08%)
Hepatobiliary disorders
Veno-occlusive disease † 1	4/142 (2.82%)	4
Immune system disorders
Graft failure † 1	6/142 (4.23%)	6
Graft versus host disease † 1	1/142 (0.70%)	1
Multiorgan failure † 1	1/142 (0.70%)	1
Infections and infestations
Aspergillus pneumonia † 1	1/142 (0.70%)	1
Septic shock † 1	1/142 (0.70%)	1
Respiratory, thoracic and mediastinal disorders
Pulmonary failure † 1	7/142 (4.93%)	7
Pulmonary hemorrhage † 1	1/142 (0.70%)	1
1 Term from vocabulary, CTCAE (3.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Bone Marrow Transplant
	Affected / at Risk (%)	# Events
Total	0/142 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Leo Luznik, MD
• Organization: Johns Hopkins University
• Phone: 4105027732
• EMail: luznile@jhmi.edu

Publications of Results:

Luznik L, Bolaños-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00134017
• Other Study ID Numbers: J0373; P01CA015396 ( U.S. NIH Grant/Contract ); P30CA006973 ( U.S. NIH Grant/Contract ); NA_00034100 ( Other Identifier: JHMIRB )
• First Submitted: August 22, 2005
• First Posted: August 24, 2005
• Results First Submitted: July 31, 2018
• Results First Posted: August 31, 2018
• Last Update Posted: August 31, 2018