Antithymocyte Globulin and Cyclosporine in Preventing Graft-Versus-Host Disease in Patients Undergoing Chemotherapy With or Without Radiation Therapy Followed By Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Jonsson Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00093587

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine after transplant may stop this from happening.

PURPOSE: This randomized clinical trial is studying how well giving antithymocyte globulin together with cyclosporine works in preventing graft-versus-host disease in patients who are undergoing chemotherapy with or without radiation therapy followed by donor stem cell transplant for acute lymphoblastic leukemia or acute myeloid leukemia.

Condition	Intervention
Graft Versus Host Disease Leukemia	Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Open Label, Active Control
Official Title:	Pilot Trial of Two Dose Levels of Thymoglobulin® as Part of a Myeloablative-Conditioning for a HLA Identical Matched Related Donor (MRD) Stem Cell Transplant With Cyclosporine (CsA) as Posttransplant Graft vs Host Disease (GvHD) Prophylaxis

Resource links provided by NLM:

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Radiation Therapy

Drug Information available for: Cyclophosphamide Busulfan Cyclosporine Cyclosporin

U.S. FDA Resources

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

Study Start Date:

August 2004

Detailed Description:

OBJECTIVES:

Primary

Compare the incidence of acute graft-vs-host disease (GVHD) within the first 100 days after transplantation in patients with acute lymphoblastic leukemia or acute myeloid leukemia treated with a myeloablative conditioning regimen comprising cyclophosphamide (with or without radiotherapy) and low- vs high-dose anti-thymocyte globulin followed by allogeneic HLA-matched related stem cell transplantation and cyclosporine.
Compare the incidence of serious adverse events within the first 100 days after transplantation in patients treated with these regimens.

Secondary

Compare 100-day and 6-month survival in patients treated with these regimens.
Compare the severity of acute GVHD in patients treated with these regimens.
Compare the incidence of culture-proven infections at 100 days and 6 months after transplantation in patients treated with these regimens.
Compare the incidence of mucositis, in terms of presence, severity, and duration, in patients treated with these regimens.
Compare the number of days on opiate drugs within the first 30 days after transplantation in patients treated with these regimens.
Compare the time to engraftment in patients treated with these regimens.
Compare the incidence of hospitalization within the first 6 months after transplantation, in terms of length of initial stay, cumulative total days, and number of hospitalizations, in patients treated with these regimens.
Compare the relapse rate and time to relapse in patients treated with these regimens.
Compare the incidence and severity of chronic GVHD between 100 days and 6 months after transplantation in patients treated with these regimens.

OUTLINE: This is a pilot, randomized, open-label, multicenter study.

Conditioning: All patients receive a standard myeloablative-conditioning regimen that contains cyclophosphamide IV over 2 hours per center regimen, typically on days -6 to -3. Patients also undergo total body irradiation OR receive busulfan.
Graft-versus-host disease (GVHD) prophylaxis (as part of conditioning): Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive low-dose anti-thymocyte globulin IV over 4-8 hours on days -3 to -1.
- Arm II: Patients receive high-dose anti-thymocyte globulin IV over 4-8 hours on days -5 to -1.
Allogeneic hematopoietic stem cell transplantation: Patients in both arms undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
Post-transplantation GVHD prophylaxis: Patients in both arms receive cyclosporine IV over 1-4 hours or orally twice daily beginning on day -1 and continuing until approximately day 60 followed by tapering doses until day 180 in the absence of GVHD. Patients are followed at 7, 14, 21, 30, 100, and 180 days.

PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per treatment arm) will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Confirmed diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia
- In first complete remission or second complete remission
Secondary AML allowed
HLA-A, -B, and -DRB1 identical related donor available AND must be fully matched at Class II by high-resolution molecular HLA typing (at least 4 digits)
Currently receiving a myeloablative conditioning regimen that includes cyclophosphamide
- All patients from a center should receive the same conditioning regimen throughout the study
- No fludarabine or other purine analogues (e.g. cladribine or pentostatin) as part of conditioning regimen
No uncontrolled CNS disease

PATIENT CHARACTERISTICS:

Age

18 to 55

Performance status

ECOG 0-3

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin < 2 mg/dL
ALT and/or AST ≤ 3 times normal

Renal

Creatinine < 2.0 mg/dL OR
Creatinine clearance > 50 mL/min

Cardiovascular

Ejection fraction > 40%
No severe cardiac disease

Other

Negative pregnancy test
Fertile patients must use effective contraception
No known contraindication to administration of rabbit anti-thymocyte globulin
No current drug or alcohol abuse
No significant medical or psychosocial problem or unstable disease state (including, but not limited to, morbid obesity) that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior or concurrent bone marrow transplantation from a donor who has positive serology for HIV, hepatitis B virus, hepatitis C virus, or syphilis
No IV immunoglobulin prior to engraftment
No concurrent ex vivo engineered or processed graft (CD34+ enrichment or T-cell depletion)

Chemotherapy

See Disease Characteristics
No prior or concurrent methotrexate for graft-vs-host disease prophylaxis

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Other

More than 30 days since prior experimental agents
No other concurrent investigational agents
- Enrollment in investigational studies (i.e., anti-microbial agents) allowed only for life threatening events or after exhausting other treatment modalities

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00093587

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1678

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Gary J. Schiller, MD

Jonsson Comprehensive Cancer Center

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:	CDR0000389241, UCLA-0402009-01, GENZ-SMC-101-1026
Study First Received:	October 6, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00093587 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

graft versus host disease
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)
secondary acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission

Study placed in the following topic categories:

Anti-Infective Agents
Leukemia, Lymphoid
Cyclosporine
Immunologic Factors
Cyclophosphamide
Leukemia, Myeloid, Acute
Cyclosporins
Graft Versus Host Disease
Leukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Antifungal Agents
Neoplasm Metastasis
Congenital Abnormalities
Alkylating Agents

Lymphoma
Acute Lymphoblastic Leukemia
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Immunosuppressive Agents
Homologous Wasting Disease
Antilymphocyte Serum
Lymphatic Diseases
Busulfan
Graft vs Host Disease
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders
Antirheumatic Agents

Additional relevant MeSH terms:

Anti-Infective Agents
Leukemia, Lymphoid
Cyclosporine
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Leukemia, Myeloid, Acute
Cyclosporins
Leukemia
Antifungal Agents
Therapeutic Uses
Dermatologic Agents
Alkylating Agents

Immunoproliferative Disorders
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Enzyme Inhibitors
Leukemia, Myeloid
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Lymphatic Diseases
Neoplasms
Myeloablative Agonists
Graft vs Host Disease
Antineoplastic Agents, Alkylating
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on August 13, 2009