Fludarabine, Busulfan, and Alemtuzumab Followed By Donor Stem Cell Transplant in Treating Patients With Hematological Cancer or Other Disease - Full Text View

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00625144

Purpose

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before transplant and tacrolimus before and after transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of giving fludarabine and busulfan together with alemtuzumab followed by donor stem cell transplant and to see how well it works in treating patients with hematological cancer or other disease.

Condition	Intervention	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition	Biological: alemtuzumab Drug: busulfan Drug: fludarabine phosphate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Reduced -Intensity Preparative Regimen With Fludarabine, Busulfan, And Alemtuzumab Followed By Allogeneic Hematopoietic Stem Cell Transplant For Malignant And Non-Malignant Hematological Diseases

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety and feasibility [ Designated as safety issue: Yes ]
Rate of donor engraftment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Hematopoietic engraftment [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Acute and chronic graft-versus-host disease [ Designated as safety issue: Yes ]
Relapse [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2007
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To assess the safety and feasibility of reduced-intensity preparative regimen comprising fludarabine, busulfan, and alemtuzumab followed by allogeneic hematopoietic stem cell transplantation in patients with hematological malignancies or other diseases.
To assess the rate of donor engraftment in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Reduced-intensity preparative regimen: Patients receive busulfan IV over 3 hours on days -5 and -4, fludarabine IV on days -5 to -2, and alemtuzumab IV on days -6 to -4.
Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally every 12 hours beginning on day -2 and continuing until day 30, followed by a taper.

After completion of study treatment, patients are followed periodically.

Eligibility

Ages Eligible for Study:	up to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Myelodysplastic syndromes or myeloproliferative disorders
- Acute myelogenous leukemia (AML)
  - No refractory AML
- Acute lymphoblastic leukemia (ALL)
  - No refractory ALL
- Chronic myelogenous leukemia (CML)
  - No untreated blast crisis for CML
- Multiple myeloma (MM)
- Plasma cell dyscrasia
- Lymphoproliferative disorders, including non-Hodgkin lymphoma, hairy cell leukemia, chronic lymphocytic leukemia, or Hodgkin lymphoma
  - No uncontrolled high-grade lymphoproliferative disease or lymphoma
- Non-malignant hematologic disease considered treatable with an allogeneic stem cell transplantation (SCT) including, but not limited to, bone marrow failure syndrome, hemoglobinopathy, or severe immunodeficiency states
At increased risk for treatment-related mortality as indicated by ≥ 2 of the following:
- Over 35 years of age
- Ejection fraction < 45%
- DLCO < 50% of predicted and FEV_1 50-75% of predicted
- Diabetes mellitus
- Renal insufficiency, defined by an increase in serum creatinine level of 1.5 times or decrease in glomerular filtration rate by 25%
- Prior recent history of systemic fungal infection
- Significant grade III or IV neurologic or hepatic toxicity as defined by NCI CTC toxicity from prior treatment
- AML or ALL in third or greater remission
- Diagnosed with CML or MM > 1 year ago
- Received ≥ 3 prior treatment regimens
- Has undergone prior autologous or allogeneic SCT
- No matched sibling donor available
No active CNS disease from hematological disorder
Healthy 5/6 or 6/6 related OR 5/6 or 6/6 unrelated (molecular typing for DRB1) donor available
- No contraindications for donation

PATIENT CHARACTERISTICS:

Zubrod performance status 0-2
Total bilirubin ≤ 4 times normal
AST/ALT ≤ 4 times normal
Creatinine ≤ 2 times upper limit of normal
Ejection fraction > 30%
DLCO > 40% of predicted
FEV_1 > 1.0 L of predicted
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No HIV positivity
No concurrent uncontrolled infection
No active hepatitis or cirrhosis with total bilirubin, ALT, and AST > 3 times normal
No unstable angina or uncompensated congestive heart failure (i.e., Zubrod performance status 3-4)
No severe chronic pulmonary disease requiring oxygen (i.e., Zubrod performance status 3-4)
Not hemodialysis dependent
No unstable cerebral vascular disease or hemorrhagic stroke within the past 6 months

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00625144

Locations

United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine	Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor 713-798-1297
Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: George Carrum, MD 713-441-1450

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Study Chair:

Rammurti Kamble, MD

Baylor College of Medicine

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dan L. Duncan Cancer Center at Baylor College of Medicine ( Rammurti Kamble )
Study ID Numbers:	CDR0000582339, BCM-H-19386, BCM-FAB
Study First Received:	February 27, 2008
Last Updated:	June 9, 2009
ClinicalTrials.gov Identifier:	NCT00625144 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

accelerated phase chronic myelogenous leukemia
atypical chronic myeloid leukemia
chronic myelomonocytic leukemia
juvenile myelomonocytic leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)

adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
childhood acute myeloid leukemia in remission
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory hairy cell leukemia
progressive hairy cell leukemia, initial treatment
refractory chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent adult Hodgkin lymphoma
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma

Study placed in the following topic categories:

Mantle Cell Lymphoma
Tacrolimus
Preleukemia
Hemorrhagic Disorders
Lymphoma, Large-Cell, Anaplastic
Neoplasm Metastasis
Thrombocythemia, Hemorrhagic
Myelodysplastic Myeloproliferative Disease
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Blood Coagulation Disorders
Leukemia, Myeloid
Waldenstrom Macroglobulinemia

Plasmacytoma
Leukemia, Myeloid, Accelerated Phase
Chronic Myelogenous Leukemia
Fludarabine
Lymphoma, Non-Hodgkin
Immunologic Factors
Precancerous Conditions
Blood Protein Disorders
Lymphoma, Follicular
Sezary Syndrome
Lymphoblastic Lymphoma
Lymphoma, B-Cell
Leukemia
Cutaneous T-cell Lymphoma
Lymphoma, T-Cell

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Precancerous Conditions
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Paraproteinemias
Tacrolimus
Hemostatic Disorders
Leukemia
Preleukemia
Pathologic Processes
Hemorrhagic Disorders

Therapeutic Uses
Alemtuzumab
Syndrome
Lymphoma, Large-Cell, Immunoblastic
Cardiovascular Diseases
Alkylating Agents
Lymphoma
Disease
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Vascular Diseases

ClinicalTrials.gov processed this record on September 04, 2009