ALBUM: Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States

• Sponsor: University of Arizona (Other)
• Overall Status: Completed
• CT.gov ID: NCT00997386
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 76
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to look at whether the combination of lower-dose chemotherapy with two chemotherapy (anti-cancer) drugs, called busulfan and melphalan, and an antibody medication called alemtuzumab (Campath®), can prevent rejection of donor blood stem cells so that those cells take hold and build a healthy new blood cell factory after transplant. The study will also look at the safety of the combination of drugs and of the transplant of peripheral blood stem cells from a healthy relative or an unrelated donor.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Neoplasms; Multiple Myeloma; Anemia, Aplastic; Hemoglobinuria, Paroxysmal; Myelofibrosis	Drug: busulfan, and melphalan, and alemtuzumab	Phase 2

Detailed Description

Transplantation of related or unrelated allogeneic peripheral blood stem cells (PBSCs) after administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab will be associated with satisfactory engraftment and acceptable post-transplant non-relapse mortality.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT) for Treatment of Hematologic Malignancies and Hematopoietic Failure States
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: busulfan, and melphalan, and alemtuzumab Three drug regimen using busulfan, and melphalan, and alemtuzumab.	Drug: busulfan, and melphalan, and alemtuzumab; intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). intravenous melphalan 100 mg/m2 on day -3. intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.; Other Names: Busulfan (Busulfex®), Melphalan (Alkeran®) Alemtuzumab (Campath®)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT). [Day +100]

   To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT).

Secondary Outcome Measures

1. Number of Participants With Relapse-free Survival. [Day +100]

   To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.

2. Number of Participants With Event-free Survival. [Day +100]

   To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.

3. Number of Participants With Overall Survival. [Day +100]

   To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age 50 to 75 years or age 18 to 49 with one or more of these risk factors: prior autologous, allogeneic or syngeneic HCT (Hematopoietic cell transplantation); not in first complete remission or first chronic phase; and/or presence of one or more medical conditions that would place the subject at high risk such as heart and kidney disease.

• Subjects with hematologic cancers must have received at least one previous course of chemotherapy or biological therapy. In other words, the subject cannot enroll in this trial for initial treatment of the disease.

• Availability of a healthy related or unrelated volunteer allogeneic donor.

Exclusion Criteria:

• Eligible for another study or standard of care treatment that offers higher probability of cure or long-term control of subject's disease.

• Severe abnormal function of organs such as heart, kidneys, liver.

• Untreated or progressive central nervous system involvement by the disease.

• Subject is pregnant or breast-feeding.

• Performance score is below 50: at the least, requires considerable assistance and frequent medical care.

• Positive for the HIV [AIDS] virus

• Life expectancy less than 12 weeks with conventional treatments.

• For subjects capable of having children, refusal to practice birth control while on this study and for at least 12 months after PBSCT or after stopping post-transplant immunosuppressive treatments, whichever occurs later.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Medical Center and UMC-North Clinic	Tucson	Arizona	United States	85719

Sponsors and Collaborators

• University of Arizona

Investigators

• Principal Investigator: Andrew M Yeager, MD, University of Arizona

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Arizona
• ClinicalTrials.gov Identifier: NCT00997386
• Other Study ID Numbers: 09-0679-04
• First Posted: Oct 19, 2009
• Last Update Posted: Sep 9, 2019
• Last Verified: Sep 1, 2019

• Keywords provided by University of Arizona: Hematologic malignancies; lymphoma, leukemia, MDS (myelodysplastic syndrome); reduced-intensity preparative regimen; allogeneic peripheral blood stem cell transplant; myelofibrosis or other myeloproliferative syndromes
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms; Hematologic Neoplasms; Hemoglobinuria; Primary Myelofibrosis; Anemia, Aplastic; Hemoglobinuria, Paroxysmal; Melphalan; Busulfan; Alemtuzumab

Study Results

Participant Flow

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Period Title: Overall Study
STARTED	16
COMPLETED	9
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 43.8%
>=65 years	9 56.3%
Sex: Female, Male (Count of Participants)
Female	5 31.3%
Male	11 68.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 12.5%
Not Hispanic or Latino	14 87.5%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT).
Description	To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT).
Time Frame	Day +100

Outcome Measure Data

Analysis Population Description

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Measure Participants	0

2. Secondary Outcome

Title	Number of Participants With Relapse-free Survival.
Description	To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time Frame	Day +100

Outcome Measure Data

Analysis Population Description

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment.

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Measure Participants	0

3. Secondary Outcome

Title	Number of Participants With Event-free Survival.
Description	To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time Frame	Day +100

Outcome Measure Data

Analysis Population Description

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Measure Participants	0

4. Secondary Outcome

Title	Number of Participants With Overall Survival.
Description	To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.
Time Frame	Day +100

Outcome Measure Data

Analysis Population Description

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
Measure Participants	0

Adverse Events

Arm/Group Title	Busulfan, and Melphalan, and Alemtuzumab
Arm/Group Description	Three drug regimen using busulfan, and melphalan, and alemtuzumab. Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT). Intravenous melphalan 100 mg/m2 on day -3. Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.
All Cause Mortality
	Busulfan, and Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	7/16 (43.8%)
Serious Adverse Events
	Busulfan, and Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	3/16 (18.8%)
Gastrointestinal disorders
Pneumatosis cystoides intestinalis	1/16 (6.3%)
Abdominal Pain	1/16 (6.3%)
General disorders
Fever	1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Busulfan, and Melphalan, and Alemtuzumab
	Affected / at Risk (%)	# Events
Total	16/16 (100%)
Blood and lymphatic system disorders
Hypoalbuminemia	2/16 (12.5%)
Alkaline phosphatase	2/16 (12.5%)
Hyperbilirubinemia	2/16 (12.5%)
Blood/Bone marrow - other	5/16 (31.3%)
Hypocalcemia	1/16 (6.3%)
Creatinine	10/16 (62.5%)
Edema	9/16 (56.3%)
Neutropenia	11/16 (68.8%)
Flushing	2/16 (12.5%)
Hemoglobin	11/16 (68.8%)
Bleeding - other	3/16 (18.8%)
Leukocytes (total WBC)	16/16 (100%)
Lymphatics - other	2/16 (12.5%)
Hypomagnesemia	15/16 (93.8%)
Neutrophils/Granulocytes	13/16 (81.3%)
Petichiae/Purpura	1/16 (6.3%)
Hypophosphatemia	1/16 (6.3%)
Platelets	11/16 (68.8%)
Hypernatremia	1/16 (6.3%)
Hyponatremia	2/16 (12.5%)
Cardiac disorders
Cardiac arrhythmia	2/16 (12.5%)
Cardiac - general	3/16 (18.8%)
Pulmonary hypertension	1/16 (6.3%)
Atrial fibrillation	3/16 (18.8%)
Tachycardia	4/16 (25%)
Ventricular arrhythmia	1/16 (6.3%)
Endocrine disorders
Hyperglycemia	4/16 (25%)
Eye disorders
Dry eye	4/16 (25%)
Blurred vision	1/16 (6.3%)
Gastrointestinal disorders
Infectious colitis	1/16 (6.3%)
Constipation	6/16 (37.5%)
Diarrhea	15/16 (93.8%)
Abdominal bloating	2/16 (12.5%)
Esophagitis	1/16 (6.3%)
Gastrointestinal - other	11/16 (68.8%)
Dyspepsia	3/16 (18.8%)
Hemorrhoids	1/16 (6.3%)
Nausea	16/16 (100%)
Dysgeusia	1/16 (6.3%)
Dysarthria	1/16 (6.3%)
Vomiting	11/16 (68.8%)
General disorders
Confusion	2/16 (12.5%)
Dizziness	5/16 (31.3%)
Fatigue	14/16 (87.5%)
Fever	10/16 (62.5%)
Hypertension	11/16 (68.8%)
Hypotension	4/16 (25%)
Insomnia	8/16 (50%)
Pain	16/16 (100%)
Prutitis	5/16 (31.3%)
Rigors/chills	16/16 (100%)
Somnolence/depressed level of consciousness	1/16 (6.3%)
Syncope	1/16 (6.3%)
Hepatobiliary disorders
Hepatobiliary/pancreas - other	1/16 (6.3%)
Infections and infestations
Infection	11/16 (68.8%)
Metabolism and nutrition disorders
Anorexia	4/16 (25%)
Metabolic - other	7/16 (43.8%)
Weight gain	2/16 (12.5%)
Weight loss	2/16 (12.5%)
Musculoskeletal and connective tissue disorders
Musculoskeletal - weakness/other	3/16 (18.8%)
Nervous system disorders
Dysphagia	4/16 (25%)
Gait disturbance	3/16 (18.8%)
Neurology - other	3/16 (18.8%)
Neuropathy	2/16 (12.5%)
Seizure	1/16 (6.3%)
Tremor	2/16 (12.5%)
Psychiatric disorders
Anxiety	10/16 (62.5%)
Depression	3/16 (18.8%)
Psychosis	2/16 (12.5%)
Renal and urinary disorders
Bladder spasms	1/16 (6.3%)
Kidney perforation	1/16 (6.3%)
Renal failure	2/16 (12.5%)
Renal/Genitourinary - other	5/16 (31.3%)
Dysuria	1/16 (6.3%)
Urticaria	4/16 (25%)
Reproductive system and breast disorders
Sexual/reproductive function - other	1/16 (6.3%)
Vaginal discharge	1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory Acidosis	1/16 (6.3%)
Adult Respiratory Distress Syndrome	2/16 (12.5%)
Respiratory Alkalosis	1/16 (6.3%)
Allergic rhinitis	1/16 (6.3%)
Cough	11/16 (68.8%)
Dyspnea	10/16 (62.5%)
Hypoxia	2/16 (12.5%)
Sinus reaction	1/16 (6.3%)
Pneumonitis/Pulmonary infiltrates	3/16 (18.8%)
Pulmonary/Upper respiratory - other	3/16 (18.8%)
Skin and subcutaneous tissue disorders
Skin - other	6/16 (37.5%)
Dry mouth	4/16 (25%)
Dry skin	2/16 (12.5%)
Alopecia	4/16 (25%)
Mucositis/stomatitis	14/16 (87.5%)
Rash	3/16 (18.8%)
Vascular disorders
Vascular - other	4/16 (25%)

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.