Anti-CD45 Monoclonal Antibody, Cytarabine, Cyclophosphamide, and Total-Body Irradiation With or Without Alemtuzumab in Treating Patients Undergoing a Donor Stem Cell Transplant For Advanced Leukemia or Other Hematologic Cancer - Full Text View

Sponsored by:	Baylor College of Medicine
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00601380

Purpose

RATIONALE: Giving anti-CD45 monoclonal antibody, alemtuzumab, chemotherapy, and radiation therapy before a donor peripheral blood stem cell transplant or bone marrow stem cell transplant helps stop the growth of cancer cells and stops the patient's immune system from rejecting the donor's stem cells.

Donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase I trial is studying the side effects of giving anti-CD45 monoclonal antibody together with cytarabine, cyclophosphamide, and total-body irradiation with or without alemtuzumab followed by a donor stem cell transplant and to see how well it works in treating patients with relapsed or resistant leukemia or other hematologic cancer.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Biological: alemtuzumab Biological: anti-CD45 monoclonal antibody Drug: cyclophosphamide Drug: cytarabine Radiation: total-body irradiation	Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Radiation Therapy

Drug Information available for: Cyclophosphamide Cytarabine hydrochloride Campath Alemtuzumab Immunoglobulins Cytarabine Globulin, Immune

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	PHASE I/II STUDY OF ANTI-HUMAN CD45 MONOCLONAL ANTIBODIES IN PATIENTS WITH ADVANCED LEUKEMIA PRIOR TO ALLOGENEIC STEM CELL TRANSPLANTATION

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

Primary Outcome Measures:

Toxicity by NCI CTCAE criteria [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Effects of anti-CD45 on normal hematopoiesis and on complement levels [ Designated as safety issue: No ]
Effects of anti-CD45 on leukemic blast cells [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	February 2003
Estimated Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Preparative regimen 1: Experimental (For HLA-identical or 5/6 matched related donors): Patients receive anti-CD45 monoclonal antibody IV on days -5 to -2, cytarabine IV twice daily on days -7 to -5, cyclophosphamide IV on days -7 and -6. Patients also undergo total body irradiation twice daily on days -4 to -1.	Biological: anti-CD45 monoclonal antibody Given IV Drug: cyclophosphamide Both drugs given IV Drug: cytarabine Both drugs given IV Radiation: total-body irradiation Given twice daily for 4 days
Preparative regimen 2: Experimental (For HLA-identical or 5/6 matched unrelated donors): Patients receive anti-CD45 monoclonal antibody, cytarabine, and cyclophosphamide and undergo total-body irradiation therapy as for patients with related donors. Patients also receive alemtuzumab IV on days -8 to -6.	Biological: alemtuzumab Given IV Biological: anti-CD45 monoclonal antibody Given IV Drug: cyclophosphamide Both drugs given IV Drug: cytarabine Both drugs given IV Radiation: total-body irradiation Given twice daily for 4 days

Detailed Description:

OBJECTIVES:

Primary

To evaluate the toxicity and the anti-tumor activity of anti-CD45 monoclonal antibody in patients with relapsed or resistant leukemia or other hematologic malignancy undergoing allogeneic stem cell transplantation.

Secondary

To describe the effects of anti-CD45 on normal hematopoiesis and on complement levels.
To describe the effects of anti-CD45 on leukemic blast cells.

OUTLINE:

Preparative regimen: Patients receive treatment based on their relationship to the stem cell donor (related or unrelated).
- HLA-identical or 5/6 matched related donors: Patients receive anti-CD45 monoclonal antibody IV on days -5 to -2, cytarabine IV twice daily on days -7 to -5, cyclophosphamide IV on days -7 and -6. Patients also undergo total body irradiation twice daily on days -4 to -1.
- HLA-identical or 5/6 matched unrelated donors: Patients receive anti-CD45 monoclonal antibody, cytarabine, and cyclophosphamide and undergo total-body irradiation therapy as above. Patients also receive alemtuzumab IV on days -8 to -6.
Allogeneic stem cell transplantation: All patients undergo peripheral blood or bone marrow stem cell infusion on day 0.
Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV beginning on day -2 and continuing as per the treating physician.

Eligibility

Ages Eligible for Study:	up to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Confirmed diagnosis of advanced leukemia or other hematologic malignancy, including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia (CML), or myelodysplastic disease
- Advanced features include any of the following:
  - Induction failure, prolonged induction beyond 6 weeks
  - Incomplete response to salvage therapy
  - CML in blast crisis or acute leukemia in chemotherapy resistant relapse
  - Secondary leukemia or secondary myelodysplastic disease
CD45 present on leukemic blasts at a level of > 95% as documented by flow cytometry
HLA identical sibling donor or 5/6 matched related donor OR fully matched or 5/6 matched unrelated donor available
No T-cell lymphoblastic lymphoma

PATIENT CHARACTERISTICS:

Lansky performance status (PS) 70-100%% or Karnofsky PS 70-100%
Life expectancy > 6 weeks (not limited by diseases other than leukemia)
No symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction < 25%)
No liver disease that on evaluation by the Principal Investigator precludes ablative radio/chemotherapy or successful transplantation
Creatinine ≤ 2 times upper limit of normal
No known allergy to rat serum products
No severe infection that on evaluation by the Principal Investigator precludes ablative radio/chemotherapy or successful transplantation
No severe personality disorder or mental illness
No documented HIV positivity
Not pregnant or lactating

PRIOR CONCURRENT THERAPY:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601380

Locations

United States, Texas
Methodist Hospital	Recruiting
Houston, Texas, United States, 77030
Contact: Marlen Dinu 832-824-4881
Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital	Recruiting
Houston, Texas, United States, 77030-2399
Contact: Marlen Dinu 832-824-4881

Sponsors and Collaborators

Baylor College of Medicine

Investigators

Study Chair:

Robert Krance, 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

Study ID Numbers:	CDR0000582390, BCM-H-12870, BCM-ADVL
Study First Received:	January 15, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00601380 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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)
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia

recurrent childhood acute myeloid leukemia
secondary acute myeloid leukemia
blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
childhood myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Antimetabolites
Acute Lymphoblastic Leukemia, Childhood
Blast Crisis
Leukemia, Lymphoid
Immunologic Factors
Hematologic Neoplasms
Precancerous Conditions
Cyclophosphamide
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia
Preleukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Alemtuzumab

Neoplasm Metastasis
Congenital Abnormalities
Alkylating Agents
Acute Lymphoblastic Leukemia
Cytarabine
Immunoglobulins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Myelodysplastic Syndromes
Leukemia, Myeloid
Antiviral Agents
Immunosuppressive Agents
Recurrence
Acute Myeloid Leukemia, Childhood
Antibodies

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Precancerous Conditions
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibodies, Monoclonal
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Alemtuzumab

Therapeutic Uses
Alkylating Agents
Cytarabine
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Antibodies
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Bone Marrow Diseases

ClinicalTrials.gov processed this record on May 06, 2009