Stem Cell Transplantation Compared With Standard Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia in First Remission

• ClinicalTrials.gov Identifier: NCT00002514
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: November 22, 2012
• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI); Medical Research Council
• Information provided by (Responsible Party): Eastern Cooperative Oncology Group

Study Description

Brief Summary:

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic or autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. It is not yet known whether stem cell transplantation is more effective than standard chemotherapy in treating acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is studying how well stem cell transplantation works compared to standard combination chemotherapy in treating patients with acute lymphoblastic leukemia in first remission.

Condition or disease	Intervention/treatment	Phase
Leukemia	Biological: sargramostim; Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: etoposide; Drug: imatinib mesylate; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: thioguanine; Drug: vincristine sulfate; Procedure: allogeneic bone marrow transplantation; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy	Phase 3

Detailed Description:

OBJECTIVES:

• Compare the duration of complete remission (CR) and survival in patients with acute lymphoblastic leukemia in first remission treated with allogeneic or autologous stem cell transplantation (SCT) vs conventional consolidation and maintenance chemotherapy.
• Compare the overall treatment outcomes in patients treated with these regimens.
• Determine the effect of imatinib mesylate given after induction therapy in Philadelphia (Ph) chromosome-positive patients in CR.
• Determine the benefit of allogeneic or autologous SCT after imatinib mesylate in Ph chromosome-positive patients.
• Determine the benefit of additional imatinib mesylate administered after allogeneic or autologous SCT in Ph chromosome-positive patients.
• Determine the minimal residual disease in Ph chromosome-positive patients before and after treatment with imatinib mesylate.
• Determine the clinical resistance to imatinib mesylate caused by BCR-ABL gene amplification or mutation in Ph chromosome-positive patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (50 and under vs over 50), time to achieve complete remission (CR) (4 weeks or less vs more than 4 weeks), and Philadelphia (Ph) chromosome status (positive vs negative).

• First induction therapy: Patients receive daunorubicin (DNR) IV over 15-30 minutes and vincristine (VCR) IV over 3-5 minutes on days 1, 8, 15, and 22; oral prednisone (PRED) once daily on days 1-28; and asparaginase (ASP) IV over 30 minutes or intramuscularly on days 17-28. Patients with CNS leukemia at presentation also receive methotrexate (MTX) intrathecally (IT) via an Ommaya reservoir weekly until the CSF is clear. Patients without CNS leukemia at presentation receive MTX IT on day 23 only.
• Second induction therapy: Beginning immediately after first induction therapy, patients receive cyclophosphamide (CTX) IV over 30 minutes on days 1, 15, and 29; cytarabine (ARA-C) IV over 30 minutes on days 1-4, 8-11, 15-18, and 22-25; and oral mercaptopurine (MP) once daily on days 1-28. Patients with CNS leukemia at presentation also undergo concurrent craniospinal irradiation. Patients without CNS leukemia at presentation receive MTX IT on days 1, 8, 15, and 22. Patients with Ph chromosome-positive status receive oral imatinib mesylate once daily for at least 28 days (days 1-28).

Patients with Ph chromosome-positive status and CR after second induction therapy proceed to group I for autologous or allogeneic stem cell transplantation (SCT). Patients with Ph chromosome-negative status and CR after second induction therapy proceed to group II.

• Group I (Ph chromosome-positive patients):

  • Autologous SCT: Patients receive high-dose consolidation/mobilization chemotherapy comprising ARA-C IV over 3 hours on days 1-3 and mitoxantrone IV immediately after ARA-C administration on days 1 and 2. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 5 and continuing until blood counts recover.

Patients then undergo peripheral blood stem cell collection or bone marrow harvesting.

Patients receive preparative therapy comprising total body irradiation twice daily (5-10 hours apart) on days -6 to -4 and high-dose etoposide (VP-16) IV over 4 hours on day -3. Male patients also undergo radiotherapy boost to the testes on day -6.

Patients undergo autologous SCT on day 0 and receive sargramostim (GM-CSF) SC once daily beginning 6 hours after the completion of SCT and continuing until blood counts recover.

• Allogeneic SCT: Patients receive the preparative regimen as in autologous SCT and then undergo allogeneic SCT on day 0. Patients receive GM-CSF as in autologous SCT.

• Post-SCT imatinib mesylate therapy: After recovery from autologous or allogeneic SCT, patients receive oral imatinib mesylate once daily. Imatinib mesylate therapy continues in the absence of disease progression or unacceptable toxicity.

  • Group II (Ph chromosome-negative patients):
• Intensification therapy: Beginning 4 weeks after the completion of the second induction therapy, patients receive high-dose MTX IV over 2 hours on days 1, 8, and 22; leucovorin calcium IV every 6 hours for 4 doses and then orally every 6 hours for 12 doses beginning 22-24 hours after each MTX infusion; and ASP IV over 30 minutes on days 2, 9, and 23.

Patients who are ≤ 50 years of age with a histocompatible donor proceed to allogeneic SCT and undergo allogeneic SCT as in group I. Patients who are ≤ 50 years of age without an appropriate donor are randomized to 1 of 2 treatment arms.

• Arm I (conventional consolidation/maintenance therapy):

  • Conventional consolidation therapy: During course 1, patients receive ARA-C IV over 30 minutes and VP-16 IV over 1 hour on days 1-5; VCR IV on days 1, 8, 15, and 22; and oral dexamethasone on days 1-28. During course 2 (which begins 4 weeks after initiation of course 1 or when blood counts recover), patients receive ARA-C and VP-16 as in course 1. During course 3 (which begins 4 weeks after initiation of course 2 or when blood counts recover), patients receive DNR IV on days 1, 8, 15, and 22; CTX IV over 30 minutes on day 29; ARA-C IV over 30 minutes on days 31-34 and 38-41; and oral thioguanine on days 29-42. During course 4 (which begins 8 weeks after initiation of course 3 or when blood counts recover), patients receive treatment as in course 2.
  • Maintenance therapy: Beginning 4 weeks after initiation of course 4 of consolidation therapy or when blood counts recover, patients receive oral MP daily; MTX orally or IV once weekly; VCR IV once every 12 weeks; and oral PRED for 5 days every 12 weeks. Maintenance therapy continues for 2.5 years after initiation of intensification therapy.
• Arm II (autologous SCT): Patients undergo autologous SCT as in group I with the exception of high-dose consolidation/mobilization chemotherapy.

Patients are followed every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 40 patients per year will be accrued for group I (Philadelphia [Ph] chromosome-positive patients) of this study. Approximately 550 patients will be accrued for group II (Ph chromosome-negative patients) of this study within 5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1929 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Randomized Trial of Autologous and Allogeneic Stem Cell Transplantation Versus Intensive Conventional Chemotherapy in Acute Lymphoblastic Leukemia in First Remission
• Study Start Date: April 1993
• Actual Primary Completion Date: December 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: Transplant; Allogeneic (if donor) or Autologous (if no donor) bone marrow transplant	Biological: sargramostim; Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: etoposide; Drug: imatinib mesylate; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: vincristine sulfate; Procedure: allogeneic bone marrow transplantation; Procedure: autologous bone marrow transplantation; Procedure: peripheral blood stem cell transplantation
Active Comparator: Conventional Consolidation/Maintenance; Consolidation/Maintenance Therapy	Drug: asparaginase; Drug: cyclophosphamide; Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: dexamethasone; Drug: etoposide; Drug: leucovorin calcium; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: thioguanine; Drug: vincristine sulfate; Radiation: radiation therapy

Outcome Measures

Primary Outcome Measures :

1. Overall Survival [ Time Frame: All patients were followed for 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 65 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed acute lymphoblastic leukemia (ALL)

  • More than 25% lymphoblasts in bone marrow

    • Patients with myeloid antigen expression AND unequivocal lymphoid immunophenotype are eligible

• Philadelphia (Ph) chromosome status determined by cytogenetics, fluorescence in situ hybridization (FISH), and/or RNA analysis

  • Patients determined to be Ph chromosome negative by cytogenetics, but positive for BCR-ABL by FISH or polymerase chain reaction are considered Ph chromosome positive
  • Patients with Ph chromosome-positive disease may be up to age 65
• No myelodysplasia or other antecedent hematologic disorder

• Patients age 50 and under must be HLA typed during induction therapy of study treatment OR provide a written explanation for not undergoing HLA typing

  • A and B typing required
  • C and DR typing done if feasible

• Allogeneic stem cell transplantation patients must meet the following criteria:

  • Appropriate HLA histocompatible donor available

    • Ph chromosome-negative patients must have HLA identical sibling
    • Ph chromosome-positive patients must have HLA identical, HLA-matched unrelated, or haploidentical related donor

• Postinduction therapy:

  • CSF negative for leukemia
  • No occult or overt leukemic meningitis
  • Documented complete remission

PATIENT CHARACTERISTICS:

Age:

• 15 to 65

Performance status:

• Induction therapy:

  • Not specified

• Postinduction therapy:

  • 0-1

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Induction therapy:

  • Direct bilirubin ≤ 2.0 mg/dL

• Postinduction therapy:

  • Direct bilirubin < 2.0 mg/dL
  • SGPT or SGOT < 3 times normal

Renal:

• Induction therapy:

  • Creatinine < 2 mg/dL

• Postinduction therapy:

  • Creatinine ≤ 2 mg/dL
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular:

• Induction and postinduction therapy:

  • No significant cardiac disease requiring digoxin and/or diuretics
  • No major ventricular dysrhythmia requiring medication
  • No ischemic heart disease requiring medication

• Postinduction therapy:

  • Cardiac ejection fraction ≥ 50% for patients under consideration for transplantation

Pulmonary:

• Induction therapy:

  • Not specified

• Postinduction therapy:

  • FEV_1 ≥ 60% of predicted for patients under consideration for transplantation
  • DLCO ≥ 50% of predicted for patients under consideration for transplantation

Other:

• Induction and postinduction therapy:

  • HIV negative
  • No concurrent organ damage or other medical problem (e.g., psychiatric disorder or drug abuse) that would preclude study therapy
  • Not pregnant

• Postinduction therapy:

  • No persistent infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent umbilical cord allogeneic transplantation

Chemotherapy:

• Not specified

Endocrine therapy:

• Prior corticosteroids for ALL allowed

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Induction and postinduction therapy:

  • No other prior therapy for ALL

• Postinduction therapy:

  • No concurrent antibiotics

Contacts and Locations

Locations

United States, Colorado

Aurora Presbyterian Hospital

Aurora, Colorado, United States, 80012

Boulder Community Hospital

Boulder, Colorado, United States, 80301-9019

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, United States, 80933

Porter Adventist Hospital

Denver, Colorado, United States, 80210

Presbyterian - St. Luke's Medical Center

Denver, Colorado, United States, 80218

St. Joseph Hospital

Denver, Colorado, United States, 80218

Rose Medical Center

Denver, Colorado, United States, 80220

CCOP - Colorado Cancer Research Program

Denver, Colorado, United States, 80224-2522

Swedish Medical Center

Englewood, Colorado, United States, 80110

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

Grand Junction, Colorado, United States, 81502

Sky Ridge Medical Center

Lone Tree, Colorado, United States, 80124

Hope Cancer Care Center at Longmont United Hospital

Longmont, Colorado, United States, 80502

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, United States, 81004

North Suburban Medical Center

Thornton, Colorado, United States, 80229

United States, Connecticut

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, United States, 06360-2875

George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus

New Britain, Connecticut, United States, 06050

United States, Illinois

Rush-Copley Cancer Care Center

Aurora, Illinois, United States, 60507

Evanston Northwestern Healthcare - Evanston Hospital

Evanston, Illinois, United States, 60201-1781

Hinsdale Hematology Oncology Associates

Hinsdale, Illinois, United States, 60521

Joliet Oncology-Hematology Associates, Limited - West

Joliet, Illinois, United States, 60435

Carle Cancer Center at Carle Foundation Hospital

Urbana, Illinois, United States, 61801

CCOP - Carle Cancer Center

Urbana, Illinois, United States, 61801

United States, Indiana

Methodist Cancer Center at Methodist Hospital

Indianapolis, Indiana, United States, 46202

Saint Anthony Memorial Health Centers

Michigan City, Indiana, United States, 46360

United States, Iowa

Cedar Rapids Oncology Associates

Cedar Rapids, Iowa, United States, 52403

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, United States, 51101

Mercy Medical Center - Sioux City

Sioux City, Iowa, United States, 51104

St. Luke's Regional Medical Center

Sioux City, Iowa, United States, 51104

United States, Massachusetts

Tufts-NEMC Cancer Center

Boston, Massachusetts, United States, 02111

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Baystate Regional Cancer Program at D'Amour Center for Cancer Care

Springfield, Massachusetts, United States, 01199

United States, Michigan

Saint Joseph Mercy Cancer Center

Ann Arbor, Michigan, United States, 48106-0995

CCOP - Michigan Cancer Research Consortium

Ann Arbor, Michigan, United States, 48106

Oakwood Cancer Center at Oakwood Hospital and Medical Center

Dearborn, Michigan, United States, 48123-2500

Genesys Hurley Cancer Institute

Flint, Michigan, United States, 48503

Hurley Medical Center

Flint, Michigan, United States, 48503

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States, 48236

Foote Hospital

Jackson, Michigan, United States, 49201

Borgess Medical Center

Kalamazooaa, Michigan, United States, 49001

West Michigan Cancer Center

Kalamazoo, Michigan, United States, 49007-3731

Bronson Methodist Hospital

Kalamazoo, Michigan, United States, 49007

Sparrow Regional Cancer Center

Lansing, Michigan, United States, 48912-1811

Seton Cancer Institute - Saginaw

Saginaw, Michigan, United States, 48601

St. John Macomb Hospital

Warren, Michigan, United States, 48093

United States, Minnesota

MeritCare Bemidji

Bemidji, Minnesota, United States, 56601

Fairview Ridges Hospital

Burnsville, Minnesota, United States, 55337

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, United States, 55433

Duluth Clinic Cancer Center - Duluth

Duluth, Minnesota, United States, 55805-1983

CCOP - Duluth

Duluth, Minnesota, United States, 55805

Miller - Dwan Medical Center

Duluth, Minnesota, United States, 55805

Fairview Southdale Hospital

Edina, Minnesota, United States, 55435

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, United States, 55432

Hutchinson Area Health Care

Hutchinson, Minnesota, United States, 55350

Meeker County Memorial Hospital

Lichfield, Minnesota, United States, 55355

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, United States, 55109

Minnesota Oncology Hematology, PA - Maplewood

Maplewood, Minnesota, United States, 55109

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, United States, 55407

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, United States, 55415

Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, United States, 55422-2900

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States, 55416

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, United States, 55379

HealthEast Cancer Care at St. Joseph's Hospital

St Paul, Minnesota, United States, 55102

Park Nicollet Cancer Center

St. Louis Park, Minnesota, United States, 55416

Regions Hospital Cancer Care Center

St. Paul, Minnesota, United States, 55101

United Hospital

St. Paul, Minnesota, United States, 55102

Ridgeview Medical Center

Waconia, Minnesota, United States, 55387

HealthEast Cancer Care at Woodwinds Health Campus

Woodbury, Minnesota, United States, 55125

Minnesota Oncology Hematology, PA - Woodbury

Woodbury, Minnesota, United States, 55125

United States, North Dakota

CCOP - MeritCare Hospital

Fargo, North Dakota, United States, 58122

MeritCare Broadway

Fargo, North Dakota, United States, 58122

United States, Ohio

Mercy Cancer Center at Mercy Medical Center

Canton, Ohio, United States, 44708

Aultman Cancer Center at Aultman Hospital

Canton, Ohio, United States, 44710-1799

Jewish Hospital Cancer Center

Cincinnati, Ohio, United States, 45236

Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106-5065

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, United States, 44109

St. Rita's Medical Center

Lima, Ohio, United States, 45801

United States, Oklahoma

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, United States, 74136

United States, Pennsylvania

Geisinger Medical Center

Danville, Pennsylvania, United States, 17822-0001

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033-0850

Drexel University College of Medicine - Center City Hahnemann Campus

Philadelphia, Pennsylvania, United States, 19102

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104-4283

Geisinger Medical Group - Scenery Park

State College, Pennsylvania, United States, 16801

Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center

Wilkes-Barre, Pennsylvania, United States, 18711

United States, South Dakota

Avera Cancer Institute

Sioux Falls, South Dakota, United States, 57105

Medical X-Ray Center, PC

Sioux Falls, South Dakota, United States, 57105

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States, 57117-5039

United States, Tennessee

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States, 37232-6838

United States, Wisconsin

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, United States, 54601

Dean Medical Center - Madison

Madison, Wisconsin, United States, 53717

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, United States, 53792-6164

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States, 54449

Froedtert Hospital and Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226-3596

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States, 53226

Marshfield Clinic - Indianhead Center

Rice Lake, Wisconsin, United States, 54868

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Medical Research Council

Investigators

• Study Chair: Jacob M. Rowe, MD; Rambam Health Care Campus
• Principal Investigator: Mark R. Litzow, MD; Mayo Clinic
• Study Chair: Antony H. Goldstone, FRCP; University College London Hospitals

More Information

Publications of Results:

Moorman AV, Schwab C, Ensor HM, Russell LJ, Morrison H, Jones L, Masic D, Patel B, Rowe JM, Tallman M, Goldstone AH, Fielding AK, Harrison CJ. IGH@ translocations, CRLF2 deregulation, and microdeletions in adolescents and adults with acute lymphoblastic leukemia. J Clin Oncol. 2012 Sep 1;30(25):3100-8. doi: 10.1200/JCO.2011.40.3907. Epub 2012 Jul 30.

Sive JI, Buck G, Fielding A, Lazarus HM, Litzow MR, Luger S, Marks DI, McMillan A, Moorman AV, Richards SM, Rowe JM, Tallman MS, Goldstone AH. Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII/ECOG2993 trial. Br J Haematol. 2012 May;157(4):463-71. doi: 10.1111/j.1365-2141.2012.09095.x. Epub 2012 Mar 13.

Patel B, Rai L, Buck G, Richards SM, Mortuza Y, Mitchell W, Gerrard G, Moorman AV, Duke V, Hoffbrand AV, Fielding AK, Goldstone AH, Foroni L. Minimal residual disease is a significant predictor of treatment failure in non T-lineage adult acute lymphoblastic leukaemia: final results of the international trial UKALL XII/ECOG2993. Br J Haematol. 2010 Jan;148(1):80-9. doi: 10.1111/j.1365-2141.2009.07941.x. Epub 2009 Oct 26.

Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood. 2009 May 7;113(19):4489-96. doi: 10.1182/blood-2009-01-199380. Epub 2009 Feb 24.

Mansour MR, Sulis ML, Duke V, Foroni L, Jenkinson S, Koo K, Allen CG, Gale RE, Buck G, Richards S, Paietta E, Rowe JM, Tallman MS, Goldstone AH, Ferrando AA, Linch DC. Prognostic implications of NOTCH1 and FBXW7 mutations in adults with T-cell acute lymphoblastic leukemia treated on the MRC UKALLXII/ECOG E2993 protocol. J Clin Oncol. 2009 Sep 10;27(26):4352-6. doi: 10.1200/JCO.2009.22.0996. Epub 2009 Jul 27.

Marks DI, Paietta EM, Moorman AV, Richards SM, Buck G, DeWald G, Ferrando A, Fielding AK, Goldstone AH, Ketterling RP, Litzow MR, Luger SM, McMillan AK, Mansour MR, Rowe JM, Tallman MS, Lazarus HM. T-cell acute lymphoblastic leukemia in adults: clinical features, immunophenotype, cytogenetics, and outcome from the large randomized prospective trial (UKALL XII/ECOG 2993). Blood. 2009 Dec 10;114(25):5136-45. doi: 10.1182/blood-2009-08-231217.

Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood. 2008 Feb 15;111(4):1827-33. Epub 2007 Nov 29.

Paietta E, Li X, Richards S, et al.: Implications for the use of monoclonal antibodies in future adult ALL trials: analysis of antigen expression in 505 B-lineage (B-Lin) ALL patients (pts) on the MRC UKALLXII/ECOG2993 Intergroup trial. [Abstract] Blood 112 (11): A-1907, 2008.

Patel B, Richards SM, Rowe JM, Goldstone AH, Fielding AK. High incidence of avascular necrosis in adolescents with acute lymphoblastic leukaemia: a UKALL XII analysis. Leukemia. 2008 Feb;22(2):308-12. Epub 2007 Nov 8.

Rowe JM, Buck G, Moorman AV, et al.: Standard consolidation/maintenance chemotherapy is consistently superior to a single autologous transplant for adult patients with acute lymphoblastic leukemia: results of the international ALL trial (MRC UKALL XII/ECOG E2993). [Abstract] Blood 112 (11): A-3314, 2008.

Fielding AK, Richards SM, Chopra R, Lazarus HM, Litzow MR, Buck G, Durrant IJ, Luger SM, Marks DI, Franklin IM, McMillan AK, Tallman MS, Rowe JM, Goldstone AH; Medical Research Council of the United Kingdom Adult ALL Working Party; Eastern Cooperative Oncology Group. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007 Feb 1;109(3):944-50. Epub 2006 Oct 10.

Fielding AK, Richards SM, Lazarus HM, et al.: Does imatinib change the outcome in Philapdelphia chromosome positive acute lymphoblastic leukaemia in adults? Data from the UKALLXII/ECOG2993 study. [Abstract] Blood 110 (11): A-8, 2007.

Juric D, Lacayo NJ, Ramsey MC, Racevskis J, Wiernik PH, Rowe JM, Goldstone AH, O'Dwyer PJ, Paietta E, Sikic BI. Differential gene expression patterns and interaction networks in BCR-ABL-positive and -negative adult acute lymphoblastic leukemias. J Clin Oncol. 2007 Apr 10;25(11):1341-9. Epub 2007 Feb 20.

Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, Vance GH, Cherry AM, Higgins RR, Fielding AK, Foroni L, Paietta E, Tallman MS, Litzow MR, Wiernik PH, Rowe JM, Goldstone AH, Dewald GW; Adult Leukaemia Working Party, Medical Research Council/National Cancer Research Institute. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007 Apr 15;109(8):3189-97. Epub 2006 Dec 14.

Lazarus HM, Richards SM, Chopra R, Litzow MR, Burnett AK, Wiernik PH, Franklin IM, Tallman MS, Cook L, Buck G, Durrant IJ, Rowe JM, Goldstone AH; Medical Research Council (MRC)/National Cancer Research Institute (NCRI) Adult Leukaemia Working Party of the United Kingdom and the Eastern Cooperative Oncology Group. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood. 2006 Jul 15;108(2):465-72. Epub 2006 Mar 23.

Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16.

Goldstone AH, Lazarus HJ, Richards SM, et al.: The outcome of 551 1st CR transplants in adult ALL from the UKALL XII/ECOG 2993 study. [Abstract] Blood 104 (11): A-615, 2004.

Lazarus HM, Richards SM, Chopra R, et al.: Adult patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) leukemia at diagnosis may attain durable complete remissions (CR). Results from the International ALL Trial (MRC UKALL-XII/ECOG E2993) . [Abstract] Blood 104 (11): A-4484, 2004.

Goldstone AH, Chopra R, Buck G, et al.: The outcome of 267 Philadelphia positive adults in the international UKALL12/ECOG E 2993 study. Final analysis and the role of allogeneic transplant in those under 50 years. [Abstract] Blood 102 (11 Pt 1): A-268, 2003.

Ferrando AA, Neuberg D, Dodge RK, et al.: Adult T-cell ALL patients whose lymphoblasts express the HOX11 oncogene have an excellent prognosis when treated with chemotherapy and are not candidates for allogeneic bone marrow transplantaton in first remission. [Abstract] Blood 100 (11 pt 1): A-578, 2002.

Paietta E, Kim H, Racevskis J, et al.: Immunophenotypic characteristics, but not age or secondary cytogenetic changes, affect response and survival of BCR/ABL positive adult acute lymphoblastic leukemia (ALL): ECOG/MRC Intergroup trial, E2993. [Abstract] Blood 100 (11 pt 1): A-2990, 2002.

Goldstone AH, Prentice HG, Durrant J, et al.: Allogeneic transplant (related or unrelated donor) Is the preferred treatment for adult Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL). Results from the international ALL trial (MRC UKALLXII/ECOG E2993). [Abstract] Blood 98 (11 Pt 1): A-3556, 2001.

Paietta E, Kim H, Rowe JM, et al.: Prognostic significance of immunophenotyping and cytogenetics in adult acute lymphoblastic leukemia (ALL): interim analysis of ECOG/MRC phase III intergroup trial, E2993. [Abstract] Blood 98 (11 Pt 1): A-3494, 2001.

Rowe JM, Richards SM, Burnett AK, et al.: Favorable results of allogeneic bone marrow transplantation (BMT) for adults with Philadelphia (Ph)-chromosome-negative acute lymphoblastic leukemia (ALL) in first complete remission (CR): results from the international ALL trial (MRC UKALL XII/ECOG E2993). [Abstract] Blood 98 (11 Pt 1): A-2009, 2001.

Goldstone AH, Richards S, Wiernik PH, et al.: Philadelphia chromosome positive patients with adult acute lymphoblastic leukemia (ALL). Early results from the international ALL trial. [Abstract] Blood 94 (suppl 1): 3071a, 1999.

Rowe JM, Richards S, Wiernik PH, et al.: Allogenic bone marrow transplantation (BMT) for adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR): early results from the international ALL trial. [Abstract] Blood 94 (suppl 1): 732a, 1999.

Paietta E, Racevskis J, Neuberg D, Rowe JM, Goldstone AH, Wiernik PH. Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993. Eastern Cooperative Oncology Group/Medical Research Council. Leukemia. 1997 Nov;11(11):1887-90.

Other Publications:

Wang H, Chen XQ, Geng QR, Liu PP, Lin GN, Xia ZJ, Lu Y. Induction therapy using the MRC UKALLXII/ECOG E2993 protocol in Chinese adults with acute lymphoblastic leukemia. Int J Hematol. 2011 Aug;94(2):163-168. doi: 10.1007/s12185-011-0891-y. Epub 2011 Jul 6.

Goldstone AH. Transplants in Adult ALL--? Allo for everyone. Biol Blood Marrow Transplant. 2009 Jan;15(1 Suppl):7-10. doi: 10.1016/j.bbmt.2008.11.017. Review.

Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A, Rowe J, Webb D. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer. 2007 Mar;48(3):254-61.

Paietta E, Ferrando AA, Neuberg D, Bennett JM, Racevskis J, Lazarus H, Dewald G, Rowe JM, Wiernik PH, Tallman MS, Look AT. Activating FLT3 mutations in CD117/KIT(+) T-cell acute lymphoblastic leukemias. Blood. 2004 Jul 15;104(2):558-60. Epub 2004 Mar 25.

Ferrando AA, Neuberg D, Dodge RK, et al.: Adult T-cell ALL patients whose lymphoblasts express the HOX11 oncogene have an excellent prognosis when treated with chemotherapy and are not candidates for allogeneic bone marrow transplantaton in first remission. [Abstract] Blood 100 (11 pt 1): A-578, 2002.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR, Lazarus H, Luger SM, Marks DI, McMillan AK, Moorman AV, Patel B, Paietta E, Tallman MS, Goldstone AH. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood. 2014 Feb 6;123(6):843-50. doi: 10.1182/blood-2013-09-529008. Epub 2013 Nov 25.

Van Vlierberghe P, Ambesi-Impiombato A, De Keersmaecker K, Hadler M, Paietta E, Tallman MS, Rowe JM, Forne C, Rue M, Ferrando AA. Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood. 2013 Jul 4;122(1):74-82. doi: 10.1182/blood-2013-03-491092. Epub 2013 May 17.

Marks DI, Moorman AV, Chilton L, Paietta E, Enshaie A, DeWald G, Harrison CJ, Fielding AK, Foroni L, Goldstone AH, Litzow MR, Luger SM, McMillan AK, Racevskis J, Rowe JM, Tallman MS, Wiernik P, Lazarus HM. The clinical characteristics, therapy and outcome of 85 adults with acute lymphoblastic leukemia and t(4;11)(q21;q23)/MLL-AFF1 prospectively treated in the UKALLXII/ECOG2993 trial. Haematologica. 2013 Jun;98(6):945-52. doi: 10.3324/haematol.2012.081877. Epub 2013 Jan 24.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00002514
• Obsolete Identifiers: NCT00222586
• Other Study ID Numbers: CDR0000078099; E2993; MRC-LEUK-UKALL-XII; EST-4491
• First Posted: January 27, 2003
• Last Update Posted: November 22, 2012
• Last Verified: August 2007

Keywords provided by Eastern Cooperative Oncology Group:

adult acute lymphoblastic leukemia in remission

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leucovorin; Cytarabine; Dexamethasone; Prednisone; Cyclophosphamide; Methotrexate; Etoposide; Vincristine; Imatinib Mesylate; Daunorubicin; Asparaginase; Mercaptopurine; Thioguanine; Sargramostim; Levoleucovorin; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents