Allo BMT Using Matched Related/Unrelated Donors With FluBu and HiCY

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT00809276
• Collaborator: M.D. Anderson Cancer Center (Other), Fred Hutchinson Cancer Center (Other), Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 92
• Locations: 3
• Duration (Months): 31
• Patients Per Site: 30.7
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this research is to find the most effective and least toxic way to prevent GVHD after BMT.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; Multiple Myeloma; Leukemia; Myelodysplastic Syndrome	Drug: Busulfan, Fludarabine, Cytoxan	Phase 1/Phase 2

Detailed Description

A person who has cancer of the blood or lymph glands can be treated by bone marrow transplantation (BMT). BMT has developed over several decades of research on both animal and human subjects as an effective treatment of various malignant and nonmalignant hematologic diseases. Many hematologic malignancies can be successfully treated with a combination of high-dose chemotherapy or chemo-radiotherapy and transplantation of allogeneic bone marrow or peripheral blood stem cells (alloBMT)

However, a possible side effect of BMT is graft versus host disease (GVHD). GVHD occurs when cells of the donor's immune system, which are present in the bone marrow, attack the BMT recipient's normal tissue. Prevention of GVHD is important for the success of the bone marrow transplant. This research is being done to find the most effective and least toxic way to prevent GVHD after BMT

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Trial of Allogeneic BMT for Hematologic Malignancies Using HLA-matched Related or Unrelated Donors With Fludarabine and IV Busulfan as Pre-transplant Conditioning Followed by Post-transplant Immunosuppression With High-dose Cyclophosphamide
• Study Start Date: May 1, 2009
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Outcome Measures

Primary Outcome Measures

1. To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD [1 year]

   Percentage of participants with grade III-IV acute graft versus host disease (GVHD). GVHD is graded on a combination of skin symptoms (rash), gut symptoms (diarrhea), and liver symptoms (using a lab test called bilirubin). Grades range from I to IV, where I is the least severe and IV is the most severe.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients ages between 0 to and 65 years of age.

• Patient must have a genotypically HLA-identical sibling, a phenotypically matched first-degree relative or an unrelated matched donor.

• Acute lymphocytic leukemia (ALL) in CR1 with high risk features

• Acute myeloid leukemia (AML) in CR1 with high risk features defined as:

1. Greater than 1 cycle of induction therapy required to achieve remission, ii. Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML iii. Presence of Flt3 mutations or internal tandem duplications, iv. FAB M6 or M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia, or v. Complex karyotype [> 3 abnormalities]

• Acute Leukemias in 2nd or greater remission

• Refractory or Relapsed AML

• AML transformed from MDS

• Myelodysplastic syndrome (MDS) beyond refractory anemia

• Chronic myeloid leukemia (CML)

• Chronic myelomonocytic leukemia

• Philadelphia-negative myeloproliferative disorder

• Relapsed chemotherapy-sensitive Hodgkin's or Non-Hodgkin's lymphoma

• Multiple Myeloma-Stage III

Exclusion Criteria:

• Prior autologous or allogeneic stem cell transplant.

• Performance status greater than 2

• Active infection.

• Inadequate cardiac function; arrythmias or symptomatic cardiac disease.

• Inadequate pulmonary function; FEV1, FVC, DLCO <50% of predicted

• Inadequate Serum creatinine clearance <60

• InadequatebHepatic function

• Positive serology for HIV-1, 2 or HTLV-1, 2.

• Pregnancy. Female patient must have negative pregnancy test

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Sydney Kimmel Comprehensive Cancer center	Baltimore	Maryland	United States	21231
2	Marcos deLima, MD	Houston	Texas	United States	77030
3	Paul V. O'Donnell, M.D., Ph.D.	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• M.D. Anderson Cancer Center
• Fred Hutchinson Cancer Center
• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Chair: Leo Luznik, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00809276
• Other Study ID Numbers: J0844; NA_00017193
• First Posted: Dec 17, 2008
• Last Update Posted: Feb 16, 2015
• Last Verified: Jan 1, 2015

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Acute lymphocytic leukemia (ALL); Acute myeloid leukemia (AML); Acute Leukemia; Refractory or Relapsed AML; Myelodysplastic syndrome (MDS); Chronic myeloid leukemia (CML); Chronic myelomonocytic leukemia; Hodgkin's Lymphoma; Non-Hodgkin's lymphoma; Philadelphia-negative myeloproliferative disorder; Hematologic Malignancies; Transplantation; Busulfan; Fludarabine; Cytoxan; Bone Marrow; Allogeneic; Related donor; unrelated donor
• Additional relevant MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Preleukemia; Myelodysplastic Syndromes; Cyclophosphamide; Busulfan; Fludarabine

Study Results

Participant Flow

Arm/Group Title	BuFlu Transplant
Arm/Group Description	Myeloablative bone marrow transplant with busulfan and fludarabine conditioning Post-transplantation cyclophosphamide as single-agent graft-versus-host-disease prophylaxis
Period Title: Overall Study
STARTED	92
COMPLETED	92
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	BuFlu Transplant
Arm/Group Description	Myeloablative bone marrow transplant with busulfan and fludarabine conditioning Post-transplantation cyclophosphamide as single-agent graft-versus-host-disease prophylaxis
Overall Participants	92
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	49
Sex: Female, Male (Count of Participants)
Female	52 56.5%
Male	40 43.5%
Region of Enrollment (participants) [Number]
United States	92 100%

Outcome Measures

1. Primary Outcome

Title	To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD
Description	Percentage of participants with grade III-IV acute graft versus host disease (GVHD). GVHD is graded on a combination of skin symptoms (rash), gut symptoms (diarrhea), and liver symptoms (using a lab test called bilirubin). Grades range from I to IV, where I is the least severe and IV is the most severe.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	BuFlu Transplant
Arm/Group Description	Myeloablative bone marrow transplant with busulfan and fludarabine conditioning Post-transplantation cyclophosphamide as single-agent graft-versus-host-disease prophylaxis
Measure Participants	92
Number (95% Confidence Interval) [percentage of participants]	15 16.3%

Adverse Events

Time Frame	Up to 100 days after bone marrow transplant.
Adverse Event Reporting Description	Systematically monitored through at least Day 60.
Arm/Group Title	BuFlu Transplant
Arm/Group Description	Myeloablative bone marrow transplant with busulfan and fludarabine conditioning Post-transplantation cyclophosphamide as single-agent graft-versus-host-disease prophylaxis
All Cause Mortality
	BuFlu Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	BuFlu Transplant
	Affected / at Risk (%)	# Events
Total	40/92 (43.5%)
Blood and lymphatic system disorders
Primary graft failure	5/92 (5.4%)
Subdural hematoma	1/92 (1.1%)
Secondary graft failure	2/92 (2.2%)
Diffuse alveolar hemorrhage	1/92 (1.1%)
Cardiac disorders
Cardiac arrest	1/92 (1.1%)
Hypotension	1/92 (1.1%)
Left ventricular systolic dysfunction	1/92 (1.1%)
Gastrointestinal disorders
Bowel obstruction	1/92 (1.1%)
Gastritis and ileitis	1/92 (1.1%)
Mucositis	19/92 (20.7%)
Infections and infestations
Infection	12/92 (13%)
Neutropenic fever	11/92 (12%)
Investigations
Death	8/92 (8.7%)
ALT elevation grade 3-4	8/92 (8.7%)
AST elevation grade 3-4	6/92 (6.5%)
Hyperbilirubinemia grade 3-4	1/92 (1.1%)
Alkaline phosphatase elevated grade 3-4	3/92 (3.3%)
Hyperuricemia	1/92 (1.1%)
Hypokalemia	1/92 (1.1%)
Renal and urinary disorders
Hemorrhagic cystitis	2/92 (2.2%)
Renal toxicity	1/92 (1.1%)
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary syndrome	1/92 (1.1%)
Skin and subcutaneous tissue disorders
Erythroderma	1/92 (1.1%)
Rash	1/92 (1.1%)
Other (Not Including Serious) Adverse Events
	BuFlu Transplant
	Affected / at Risk (%)	# Events
Total	34/92 (37%)
Gastrointestinal disorders
Mucositis	6/92 (6.5%)
Investigations
AST elevation grade 3-4	11/92 (12%)
ALT elevation grade 3-4	20/92 (21.7%)
Engraftment > Day 28	11/92 (12%)
Hyperbilirubinemia grade 3-4	7/92 (7.6%)

Limitations/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.