Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Monoclonal Antibody Therapy, Fludarabine, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Disease

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Biomarker/Laboratory analysis, Treatment Active Under 100 Other BCM-H-12472 H 12472, BCM-ACHE, NCT00056966

Objectives

Primary

1. To assess the safety and feasibility, in terms of day 100 non-relapse mortality and graft rejection, of monoclonal antibodies directed to the CD45 and CD52 antigens (alemtuzumab), fludarabine phosphate, and low-dose total-body irradiation, as a non-myeloablative preparatory regimen for patients with hematological diseases treated with allogeneic hematopoietic stem cell transplantation.

Secondary

1. Determine complete remission at day 100 in patients treated with this regimen.
2. Determine the 1-year disease-free survival in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of 1 of the following documented high-risk diseases needing allogeneic hematopoietic stem cell transplantation:
  • Acute myeloid leukemia or acute lymphoblastic leukemia, meeting 1 of the following criteria:
    • Primary refractory disease
    • Beyond first complete remission (CR1)
    • In CR1 with high risk of relapse
  • Chronic myelogenous leukemia, meeting 1 of the following criteria:
    • Accelerated phase
    • Blast crisis
    • Chronic phase and not achieving major cytogenetic response despite standard therapy
  • Chronic lymphocytic leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma meeting 1 of the following criteria:
    • Primary refractory disease
    • Beyond CR1
  • Myelodysplastic syndromes with International Prognostic Scoring System score > 0.5
  • Myeloproliferative disorders (with the exclusion of chronic myelogenous leukemia) meeting 1 of the following criteria:
    • Primary myelofibrosis with Lile score of 1 or 2
    • Polycythemia vera (PV)
    • Essential thrombocythemia transformed to AML
    • Myelofibrosis and PV “spent phase”
  • Multiple myeloma
    • Stage II-III disease
  • Severe aplastic anemia



• Must meet ≥ 1 of the following criteria that increase treatment-related mortality:
  • Age ≥ 35 years
  • Ejection fraction < 50%
  • DLCO < 50% or FEV₁/FVC < 80% of predicted value
  • Diabetes mellitus
  • Serum creatinine abnormal
  • Transaminases, alkaline phosphatase, or bilirubin 2 times upper limit of normal
  • Recent history of systemic fungal infection
  • Have undergone ≥ 3 prior treatment regimens
  • Significant grade 3 or 4 neurologic, cardiac, pulmonary, renal, or hepatic toxicity from prior treatment
  • Have undergone prior autologous or allogeneic stem cell transplantation



• Available 5/6 or 6/6 related or unrelated healthy donor by molecular typing for DRB1

Prior/Concurrent Therapy:

• See Disease Characteristics

Patient Characteristics:

• See Disease Characteristics
• Zubrod performance status 0-2
• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV-negative
• No unstable angina or uncompensated congestive heart failure
• No unstable cerebral vascular disease or recent hemorrhagic stroke (less than 6 months)
• No severe chronic pulmonary disease requiring oxygen
• No Child class C cirrhosis
• No known allergy to rat serum products

Expected Enrollment

Outcomes

Non-relapse mortality at day 100
Graft rejection at day 100

Hematopoietic engraftment and chimerism studies demonstrated donor hematopoiesis
Toxicity as assessed by NCI Common Criteria Index
Acute graft-vs-host disease (GVHD) and chronic GVHD
Relapse
Complete remission
Progression-free survival
Survival

Outline

This is a multicenter study.

Patients receive alemtuzumab IV on days -8 to -6, fludarabine phosphate IV on days -8 to -5, and anti-CD45 monoclonal antibody IV on days -5 to -2. Patients undergo a single-fraction of low-dose total-body irradiation on day -1 and an allogeneic peripheral blood or bone marrow stem cell infusion on day 0. Patients also receive tacrolimus orally or IV on days -2 to 30, followed by a taper.

Blood samples are collected at baseline and at 1, 3, 6, 9, 12, 18, and 24 months post-transplantation for immune reconstitution studies and virus-specific immunity tests. Samples are also analyzed for chimerism studies, pharmacokinetic studies, and anti-CD45 studies by flow cytometry. Additional serum samples will be collected and stored for use at a later time for the detection of human anti-rat antibodies.

After completion of study treatment, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

Dan L. Duncan Cancer Center at Baylor College of Medicine

George Carrum, MD, Protocol chair		Ph: 713-441-1450

U.S.A.
Texas
	Houston
	Methodist Hospital
		Jassmyn Carr	Ph:  713-441-1954
	Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital
		Jassmyn Carr	Ph:  713-441-1954

Registry Information
Official Title		PHASE I/II STUDY OF CD45 ANTIBODIES AND ALEMTUZUMAB CONDITIONING REGIMEN FOR ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION OF PATIENTS WITH HEMATOLOGICAL DISEASES
Trial Start Date		2002-11-23
Trial Completion Date		2013-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00056966
Date Submitted to PDQ		2007-12-13
Information Last Verified		2008-08-13