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

Alternate Title

Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	15 to 59	NCI	CALGB-C10001 CALGB-10001, NCT00039377

Objectives

1. Determine the activity of imatinib mesylate, in terms of prolonging disease-free and overall survival, in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (t[9;22] cytogenetics).
2. Determine the ability of imatinib mesylate, administered after sequential chemotherapy, initial imatinib mesylate, and peripheral blood stem cell transplantation (PBSCT), to produce or maintain a BCR-ABL-negative status by reverse transcription polymerase chain reaction in these patients.
3. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation after treatment with imatinib mesylate in these patients.
4. Determine the safety and efficacy of autologous or allogeneic PBSCT in these patients.
5. Determine the safety and efficacy of imatinib mesylate administered after autologous or allogeneic PBSCT in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed acute lymphoblastic leukemia (ALL)
  • Disease in complete or partial remission after 1 course of induction chemotherapy comprising 1 of the following:
    • Intensive 4- or 5-drug regimen on a CALGB or SWOG ALL protocol for previously untreated ALL
    • Any standard induction regimen without enrollment on a cooperative group frontline protocol
• BCR-ABL positive by reverse transcriptase-polymerase chain reaction or fluorescent in situ hybridization

  OR

• Detection of t(9;22)(q34;q22) or 3-way variant by metaphase cytogenetics
• All patients must also be enrolled on protocol CLB-9862

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent steroids except for adrenal failure
• No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)

Radiotherapy:

• No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease

Surgery:

• Not specified

Other:

• No more than 6 weeks of prior imatinib mesylate during induction therapy

Patient Characteristics:

Age:

• 15 to 59

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

Expected Enrollment

Approximately 60 patients will be accrued for this study within 1.5 years.

Outcomes

Disease-free survival and overall survival

BCR-ABL-negative status as assessed by reverse transcription polymerase chain reaction
Feasibility of peripheral blood stem cell (PBSC) collection
Safety and efficacy of autologous or allogeneic PBSC transplantation
Safety and efficacy of imatinib mesylate

Outline

This is a multicenter study.

Patients receive 1 course of front-line induction therapy on a CALGB/SWOG protocol prior to enrollment (Course I).

• Course II: Patients receive oral imatinib mesylate twice daily on days 1-28.
• Course III: Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate IV over 3 hours, and vincristine IV on days 1, 8, and 15; oral methotrexate every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and oral leucovorin calcium every 6 hours on days 3, 4, 10, 11, 17, and 18.
• Course IV: After blood counts recover after completion of course III, patients receive imatinib mesylate as in course II.
• Course V: Patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT), autologous PBSCT, or no PBSCT.
  • Allogeneic PBSCT: Beginning 3-10 days after completion of course IV, patients with an HLA-matched sibling donor undergo total body irradiation (TBI) 2-3 times daily on days -7 to -4. Patients receive etoposide IV over 4 hours on day -3. Patients then undergo PBSCT on day 0. Patients then receive graft-vs-host disease prophylaxis with tacrolimus IV continuously on days -1 to 56 (or IV continuously on days -1 to 14 and then orally or IV every 12 hours on days 15-56) followed by a taper. Patients also receive methotrexate IV on days 1, 3, and 6, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
  • Autologous PBSCT: Beginning 3-10 days after completion of course IV, patients without an HLA-matched sibling donor receive etoposide IV continuously and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC beginning on day 14 and continuing until peripheral blood stem cell (PBSC) collection is complete. Patients receive oral imatinib mesylate twice daily beginning after completion of PBSC collection and continuing until 3 days before PBSCT.

    Patients then undergo TBI 2-3 times daily on days -8 to -5. Patients receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 2 hours on day -2. Patients undergo PBSCT on day 0. Patients receive G-CSF SC beginning on day 0 and continuing until blood counts recover.

  • No PBSCT: Beginning 3-10 days after completion of course IV, patients who are not candidates for PBSCT receive etoposide IV over 4 hours and cytarabine IV over 2 hours on days 1-4. Patients also receive G-CSF SC once or twice a day beginning on day 14 and continuing until blood counts recover.

• Course VI: Patients receive oral imatinib mesylate once or twice daily beginning on day 30 posttransplantation or on day 30 if no transplantation received and continuing for at least 1 year or until patient has 2 consecutive negative reverse transcriptase-polymerase chain reaction assays at least 3 months apart or until relapse.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months for up to 10 years.

Wetzler M, Stock W, Donohue KA, et al.: Autologous stem cell transplantation (SCT) following sequential chemotherapy and imatinib for adults with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) CALGB study 10001. [Abstract] Blood 110 (11): A-2869, 2007.

Wetzler M, Stock W, Owzar K, et al.: Sequential imatinib and chemotherapy yield reverse-transcriptase polymerase chain reaction (RT-PCR)-negative peripheral stem cell collections in Philadelphia (Ph) chromosome positive acute lymphoblastic leukemia (ALL): preliminary results of CALGB 10001. [Abstract] J Clin Oncol 24 (Suppl 18): A-6549, 349s, 2006.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Meir Wetzler, MD, Protocol chair		Ph: 716-845-8447; 800-685-6825 Email: meir.wetzler@roswellpark.org

U.S.A.
Indiana
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Nattam, MD	Ph:  260-484-8830
Maine
	Bangor
	CancerCare of Maine at Eastern Maine Medical Center
		Clinical Trials Office - CancerCare of Maine	Ph:  207-973-4274
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Geoffrey Uy	Ph:  314-747-7222 800-600-3606
New York
	Buffalo
	Roswell Park Cancer Institute
		Clinical Trials Office - Roswell Park Cancer Institute	Ph:  877-275-7724
	Manhasset
	Don Monti Comprehensive Cancer Center at North Shore University Hospital
		Clinical Trials Office - Don Monti Comprehensive Cancer Center at North Shore University Hospital	Ph:  516-734-8900
	New York
	New York Weill Cornell Cancer Center at Cornell University
		Clinical Trials Office - New York Weill Cornell Cancer Center at Cornell University	Ph:  212-746-1848
North Carolina
	Kinston
	Kinston Medical Specialists
		Peter Watson, MD	Ph:  252-559-2200ext.201
	Winston-Salem
	Wake Forest University Comprehensive Cancer Center
		Clinical Trials Office - Wake Forest University Comprehensive Cancer Center	Ph:  336-713-6771
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Ohio State University Cancer Clinical Trial Matching Service	Ph:  866-627-7616
			Email: osu@emergingmed.com
South Carolina
	Charleston
	Hollings Cancer Center at Medical University of South Carolina
		Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina	Ph:  843-792-9321
Virginia
	Richmond
	Virginia Commonwealth University Massey Cancer Center
		Clinical Trials Office -Virginia Commonwealth University Massey Cancer Center	Ph:  804-628-1939

Related Information

PDQ® clinical trial CALGB-9862

Registry Information
Official Title		A Phase II Trial Of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051, IND # 61135), And Transplantation For Adults With Newly Diagnosed PH+ Acute Lymphoblastic Leukemia By The CALGB And SWOG
Trial Start Date		2002-04-15
Trial Completion Date		2008-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00039377
Date Submitted to PDQ		2002-04-12
Information Last Verified		2009-11-09
NCI Grant/Contract Number		CA31946

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