Combination Chemotherapy With or Without Monoclonal Antibody Therapy Followed by Stem Cell Transplant in Treating Patients With Acute Myeloid Leukemia - Full Text View

Sponsors and Collaborators:	Eastern Cooperative Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00049517

Purpose

RATIONALE: Giving combination chemotherapy before a stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the transplanted stem cells. When the healthy stem cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. If the patient's stem cells are to be transplanted, the patient is also treated with a monoclonal antibody, such as gemtuzumab ozogamicin, to kill any remaining cancer cells or deliver cancer-killing substances to them without harming normal cells. It is not yet known whether combination chemotherapy is more effective with or without gemtuzumab ozogamicin followed by stem cell transplant in treating acute myeloid leukemia.

PURPOSE: This randomized phase III trial is studying combination chemotherapy, gemtuzumab ozogamicin, and stem cell transplant to see how well they work compared to combination chemotherapy and peripheral stem cell transplant alone in treating patients with acute myeloid leukemia.

Condition	Intervention	Phase
Leukemia	Biological: filgrastim Biological: sargramostim Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: gemtuzumab ozogamicin	Phase III

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

Drug Information available for: Cyclophosphamide Busulfan Cytarabine hydrochloride Daunorubicin Daunorubicin hydrochloride Filgrastim Sargramostim Gemtuzumab ozogamicin Cytarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	A Phase III Trial in Adult Acute Myeloid Leukemia: Daunorubicin Dose-Intensification and Gemtuzumab-Ozogamicin Consolidation Therapy Prior to Autologous Stem Cell Transplantation

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

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Complete remission rates [ Designated as safety issue: No ]
Impact of allogeneic stem cell transplantation [ Designated as safety issue: No ]
Effect of gemtuzumab ozogamicin on in vivo purging using pathologic and molecular correlates [ Designated as safety issue: No ]
Safety [ Designated as safety issue: Yes ]

Estimated Enrollment:	830
Study Start Date:	December 2002
Estimated Primary Completion Date:	March 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (induction therapy): Active Comparator Patients receive standard-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine IV continuously on days 1-7. Patients may receive a second course of induction therapy if complete remission (CR) is not achieved after the first course.	Drug: cytarabine Given as a continuous infusion Drug: daunorubicin hydrochloride Given IV
Arm II (induction therapy): Experimental Patients receive high-dose daunorubicin IV over 10-15 minutes on days 1-3 and cytarabine as in arm I. Patients may receive a second course of induction therapy if CR is not achieved after the first course. The second course is administered as in arm I.	Drug: cytarabine Given as a continuous infusion Drug: daunorubicin hydrochloride Given IV
Arm I (conditioning/transplant): Active Comparator Patients receive conditioning comprising busulfan IV every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive sargramostim (GM-CSF) or filgrastim (G-CSF) IV or subcutaneously (SC) beginning on day 0 and continuing until blood counts recover.	Biological: filgrastim Given IV or as an injection Biological: sargramostim Given IV or as an injection Drug: busulfan Given IV Drug: cyclophosphamide Given IV
Arm II (conditioning/transplant): Experimental Patients receive gemtuzumab ozogamicin IV over 2 hours on day 1 and GM-CSF SC or IV beginning on day 10 and continuing until blood counts recover. Within 2-3 weeks after blood count recovery, patients receive conditioning and undergo autologous PBSC transplantation as in arm I.	Biological: filgrastim Given IV or as an injection Biological: sargramostim Given IV or as an injection Drug: busulfan Given IV Drug: cyclophosphamide Given IV Drug: gemtuzumab ozogamicin Given IV

Show Detailed Description

Eligibility

Ages Eligible for Study:	16 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Morphologically confirmed acute myeloid leukemia (AML) (greater than 20% blasts in the peripheral blood or marrow) meeting any of the following criteria:
- Recurrent cytogenetic translocations
  - t(8;21)(q22;q22)
  - Bone marrow eosinophil abnormalities
    - inv(16)(p13;q22)
    - t(16;16)(p13;q22)
  - 11q23 abnormalities
- Multilineage dysplasia without presence of myelodysplastic syndromes (MDS)
- Minimally differentiated AML
- AML without maturation
- AML with maturation
- AML not otherwise categorized
- Acute myelomonocytic leukemia
- Acute monocytic leukemia
- Acute erythroid leukemia
- Acute megakaryocytic leukemia
- Acute basophilic leukemia
The following types of AML are excluded:
- Recurrent cytogenetic translocations
  - Acute promyelocytic leukemia (PML) with t(15;17)(q22;q21)
  - Variant acute PML with t(v;17)
- Multilineage dysplasia with prior MDS
- Acute panmyelosis with myelofibrosis
No blastic transformation of chronic myelogenous leukemia
No secondary AML (chemotherapy-induced or evolved from MDS)
CNS disease allowed
Patients undergoing allogeneic transplantation must have a sibling donor match defined as HLA match or haplotype match with one locus mismatch on other haplotype

PATIENT CHARACTERISTICS:

Age

16 to 60

Performance status

ECOG 0-4

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin no greater than 2.0 mg/dL (unless related to Gilbert's syndrome or hemolysis)
AST less than 4 times upper limit of normal (ULN)
Alkaline phosphatase less than 4 times ULN

Renal

Creatinine no greater than 2.0 mg/dL
Creatinine clearance at least 50 mL/min

Cardiovascular

LVEF at least 45% by post-induction MUGA
No significant cardiac disease requiring active therapy (e.g., digoxin, diuretics, antiarrhythmics, or antianginal medications)

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

No prior biologic therapy

Chemotherapy

No prior cytotoxic chemotherapy for any malignancy
Prior hydroxyurea allowed

Endocrine therapy

Prior corticosteroids allowed

Radiotherapy

No prior radiotherapy for any malignancy

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049517

Show 99 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Hugo E. Fernandez, MD

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

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

Publications:

Fernandez HF, Sun Z, Bennett JM, et al.: A single dose of gemtuzumab-ozogamicin (GO) in consolidation prior to autologous transplant for younger patients with newly diagnosed acute myeloid (AML) is safe but has no effect on disease free survival: interim results of Eastern Cooperative Oncology Group study (E1900). [Abstract] Biol Blood Marrow Transplant 14 (2): A-52, 21-2, 2008.

Vance GH, Kim H, Hicks GA, Cherry AM, Higgins R, Hulshizer RL, Tallman MS, Fernandez HF, Dewald GW. Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900). Leuk Res. 2006 Sep 20; [Epub ahead of print]

Fernandez HF, Kim HT, Bennett JM, et al.: Gemtuzumab-ozogamicin (GO; mylotarg®) as part of consolidation therapy for AML before autograft: low incidence of hepatic veno-occlusive disease. [Abstract] Biol Blood Marrow Transplant 11 (2 Suppl 1): A-187, 2005.

Responsible Party:	ECOG Group Chair's Office ( Robert L. Comis )
Study ID Numbers:	CDR0000258113, ECOG-1900
Study First Received:	November 12, 2002
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00049517 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult acute basophilic leukemia
adult acute monocytic leukemia (M5b)
adult acute eosinophilic leukemia
adult acute erythroid leukemia (M6)
adult erythroleukemia (M6a)
adult pure erythroid leukemia (M6b)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)

adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
untreated adult acute myeloid leukemia
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Study placed in the following topic categories:

Antimetabolites
Leukemia, Monocytic, Acute
Daunorubicin
Immunologic Factors
Acute Myelomonocytic Leukemia
Acute Monoblastic Leukemia
Cyclophosphamide
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Anti-Bacterial Agents
Leukemia
Acute Erythroblastic Leukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Congenital Abnormalities

Alkylating Agents
Cytarabine
Immunoglobulins
Leukemia, Myeloid
Gemtuzumab
Antiviral Agents
Immunosuppressive Agents
Leukemia, Myelomonocytic, Acute
Antibodies
Leukemia, Erythroblastic, Acute
Busulfan
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Di Guglielmo's Syndrome

Additional relevant MeSH terms:

Antimetabolites
Daunorubicin
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia

Therapeutic Uses
Alkylating Agents
Cytarabine
Neoplasms by Histologic Type
Leukemia, Myeloid
Gemtuzumab
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 07, 2009