Adult Acute Lymphoblastic Leukemia in RemissionPhase 2NCT00039377
Chemotherapy, Imatinib Mesylate, and Peripheral Stem Cell Transplantation in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
A Phase 2 study testing imatinib mesylate, methotrexate and vincristine sulfate in people with Adult Acute Lymphoblastic Leukemia in Remission, run by National Cancer Institute (NCI) at 97 sites in United States.
Trial summary
This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages 15 to 59 years
- Conditions the study is for
- Adult Acute Lymphoblastic Leukemia in Remission
- What is being tested?
- imatinib mesylate, methotrexate and vincristine sulfate
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 97 sitesUnited States
- Study dates
- Apr 2002to Feb 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 59 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Unequivocal histologic diagnosis of ALL
- Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})
- Prior Therapy:
- Complete or partial remission following one course of induction chemotherapy with an intensive 4 or 5 drug regimen (with or without imatinib mesylate) on a CALGB or SWOG ALL protocol for previously untreated ALL patients
- Note: The double induction regimen of SWOG S0333 is considered to be one course of induction chemotherapy for the purpose of this eligibility criterion; therefore, patients from S0333 may be eligible for this study only after completing the entire double induction regimen
- Complete or partial remission following one course of therapy on any standard induction regimen (with or without imatinib mesylate) without prior enrollment on a cooperative group frontline protocol; in these instances, documentation of Philadelphia chromosome (Ph)+ positivity may occur outside a CALGB or SWOG laboratory
Show all 9Show fewer
- Note: CALGB institutions must enroll patients on CALGB 9862 and submission of an initial sample for the companion trial must occur at time of enrollment on CALGB C10001; enrollment on companion studies CALGB 8461 and 9665 is not required
- No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment
- Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
Who cannot join
None listed.
Trial locations and contacts
97 sites in 1 country.
97 sites in 1 country
United States97 sites
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342
Eastern Maine Medical Center
Bangor, Maine, 04401
Beverly Hospital
Beverly, Massachusetts, 01915
Montana Cancer Consortium CCOP
Billings, Montana, 59101
Northern Rockies Radiation Oncology Center
Billings, Montana, 59101
Saint Vincent Healthcare
Billings, Montana, 59101
Hematology-Oncology Centers of the Northern Rockies PC
Billings, Montana, 59102
Billings Clinic
Billings, Montana, 59107-7000
Deaconess Medical Center
Billings, Montana, 59107
Saint Joseph Medical Center
Bloomington, Illinois, 61701
Bozeman Deaconess Cancer Center
Bozeman, Montana, 59715
Bozeman Deaconess Hospital
Bozeman, Montana, 59715
Internal Medicine of Bozeman
Bozeman, Montana, 59715
Roswell Park Cancer Institute
Buffalo, New York, 14263
Saint James Community Hospital and Cancer Treatment Center
Butte, Montana, 59701
Graham Hospital Association
Canton, Illinois, 61520
Memorial Hospital
Carthage, Illinois, 62321
Cancer Center of Kansas - Chanute
Chanute, Kansas, 66720
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Chicago
Chicago, Illinois, 60637
Weiss Memorial Hospital
Chicago, Illinois, 60640
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, 43210
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, 67801
Cancer Center of Kansas - El Dorado
El Dorado, Kansas, 67042
Eureka Hospital
Eureka, Illinois, 61530
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, 46845
Galesburg Cottage Hospital
Galesburg, Illinois, 61401
Illinois CancerCare Galesburg
Galesburg, Illinois, 61401
Addison Gilbert Hospital
Gloucester, Massachusetts, 01930
Berdeaux, Donald MD (UIA Investigator)
Great Falls, Montana, 59405
Great Falls Clinic
Great Falls, Montana, 59405
Mason District Hospital
Havana, Illinois, 62644
Saint Peter's Community Hospital
Helena, Montana, 59601
Hopedale Medical Complex - Hospital
Hopedale, Illinois, 61747
Centerpoint Medical Center LLC
Independence, Missouri, 64057
Glacier Oncology PLLC
Kalispell, Montana, 59901
Kalispell Medical Oncology
Kalispell, Montana, 59901
Kalispell Regional Medical Center
Kalispell, Montana, 59901
Providence Medical Center
Kansas City, Kansas, 66112
Saint Luke's Cancer Institute
Kansas City, Missouri, 64111
Radiation Oncology Practice Corporation South
Kansas City, Missouri, 64114
Radiation Oncology Practice Corporation - North
Kansas City, Missouri, 64154
Cheshire Medical Center-Dartmouth-Hitchcock Keene
Keene, New Hampshire, 03431
Cancer Center of Kansas-Kingman
Kingman, Kansas, 67068
Kinston Medical Specialists PA
Kinston, North Carolina, 28501
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Liberty Hospital
Liberty, Missouri, 64068
Mcdonough District Hospital
Macomb, Illinois, 61455
North Shore University Hospital
Manhasset, New York, 11030
North Shore-LIJ Health System CCOP
Manhasset, New York, 11030
Loyola University Medical Center
Maywood, Illinois, 60153
Community Medical Hospital
Missoula, Montana, 59801
Montana Cancer Specialists
Missoula, Montana, 59802
Saint Patrick Hospital - Community Hospital
Missoula, Montana, 59802
Guardian Oncology and Center for Wellness
Missoula, Montana, 59804
Long Island Jewish Medical Center
New Hyde Park, New York, 11040
North Shore-LIJ Health System/Center for Advanced Medicine
New Hyde Park, New York, 11040
Weill Medical College of Cornell University
New York, New York, 10065
Cancer Center of Kansas - Newton
Newton, Kansas, 67114
Bromenn Regional Medical Center
Normal, Illinois, 61761
Community Cancer Center Foundation
Normal, Illinois, 61761
Radiation Oncology Center of Olathe
Olathe, Kansas, 66061
Oswego Hospital
Oswego, New York, 13126
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois, 61350
Ottawa Regional Hospital and Healthcare Center
Ottawa, Illinois, 61350
Radiation Oncology Practice Corporation Southwest
Overland Park, Kansas, 66210
Cancer Center of Kansas - Parsons
Parsons, Kansas, 67357
Pekin Cancer Treatment Center
Pekin, Illinois, 61554
Pekin Hospital
Pekin, Illinois, 61554
Methodist Medical Center of Illinois
Peoria, Illinois, 61603
Proctor Hospital
Peoria, Illinois, 61614
Illinois CancerCare-Peoria
Peoria, Illinois, 61615
Illinois Oncology Research Association CCOP
Peoria, Illinois, 61615
OSF Saint Francis Medical Center
Peoria, Illinois, 61637
Illinois Valley Hospital
Peru, Illinois, 61354
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, 15224-1791
Cancer Center of Kansas - Pratt
Pratt, Kansas, 67124
Perry Memorial Hospital
Princeton, Illinois, 61356
Virginia Commonwealth University
Richmond, Virginia, 23298
Frisbie Hospital
Rochester, New Hampshire, 03867
University of Rochester
Rochester, New York, 14642
Cancer Center of Kansas - Salina
Salina, Kansas, 67401
Salina Regional Health Center
Salina, Kansas, 67401
Welch Cancer Center
Sheridan, Wyoming, 82801
Saint Margaret's Hospital
Spring Valley, Illinois, 61362
Washington University School of Medicine
St Louis, Missouri, 63110
Northeastern
St. Johnsbury, Vermont, 05819
State University of New York Upstate Medical University
Syracuse, New York, 13210
Cancer Center of Kansas - Wellington
Wellington, Kansas, 67152
Associates In Womens Health
Wichita, Kansas, 67208
Cancer Center of Kansas-Wichita Medical Arts Tower
Wichita, Kansas, 67208
Cancer Center of Kansas - Main Office
Wichita, Kansas, 67214
Via Christi Regional Medical Center
Wichita, Kansas, 67214
Wichita CCOP
Wichita, Kansas, 67214
Cancer Center of Kansas - Winfield
Winfield, Kansas, 67156
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Commonwealth Hematology Oncology PC-Worcester
Worcester, Massachusetts, 01605
About this study
Official title: A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG
This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).
II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.
IV. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).
- Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).
VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.
OUTLINE:
COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to enrollment.
COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.
COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.
COURSE IV (imatinib mesylate): 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.
COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen [HLA]-matched sibling donor): 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 PO 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 subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): 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 filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO 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 filgrastim SC beginning on day 0 and continuing until blood counts recover.
COURSE Vc (no transplantation for patients who are not transplant candidates): 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 filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts recover.
COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation 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.
After completion of study treatment, patients are followed up monthly for 1 year, every 3 months for 2 years, every 6 months for 2 years, then yearly for 5 years.
- Being tested
- imatinib mesylate, methotrexate, vincristine sulfate, leucovorin calcium, peripheral blood stem cell transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
Also called CGP 57148, Gleevec, Glivec
Given PO
methotrexateDrug
Also called amethopterin, Folex, methylaminopterin, Mexate
Given IT and IV
Also called leurocristine sulfate, VCR, Vincasar PFS
Given IV
Also called CF, CFR, LV
Given IV and PO
peripheral blood stem cell transplantationProcedure or surgery
Also called PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell
Undergo PBSCT
autologous hematopoietic stem cell transplantationProcedure or surgery
Undergo autologous PBSCT
allogeneic hematopoietic stem cell transplantationProcedure or surgery
Undergo allogeneic PBSCT
total-body irradiationRadiation
Also called TBI
Undergo TBI
tacrolimusDrug
Also called FK 506, Prograf
Given IV or PO
filgrastimBiological
Also called G-CSF, Neupogen
Given SC
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
cyclophosphamideDrug
Also called CPM, CTX, Cytoxan, Endoxan
Given IV
cytarabineDrug
Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (imatinib mesylate, chemotherapy, PBSCT) | Experimental | See Detailed Description. Receives: Drug: imatinib mesylate; Drug: methotrexate; Drug: vincristine sulfate; Drug: leucovorin calcium; Procedure: peripheral blood stem cell transplantation; Procedure: autologous hematopoietic stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Radiation: total-body irradiation; Drug: tacrolimus; Biological: filgrastim; Drug: etoposide; Drug: cyclophosphamide; Drug: cytarabine; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Free Survival
Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method.
A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.
Measured: Duration of treatment (up to 10 years)
Secondary outcomes (4)
Overall Survival
Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
Measured: Duration of study (up to 10 years)
Number of Participants Who Achieved a BCR-ABL Response at 12 Months
BCR-ABL response is defined in two ways: complete molecular response (CMR) and major molecular response (MMR).
Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene
MMR is defined as Bcr-Abl (A fusion gene of the breakpoint cluster region [Bcr] gene and Abelson proto-oncogene [Abl] genes) transcript ratio ≤0.1% (≥ 3 log reduction of BCR-ABL transcripts from a standardized baseline), as detected by reverse transcriptase polymerase chain reaction [RT-PCR] (performed centrally).
Measured: 12 months
5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups
Percentage of patients who achieved a complete remission (CR) and were alive and relapse free at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Measured: 5 years from CR
5 Year Overall Survival for Autologous & Allogeneic Transplant Groups
Percentage of patients who were alive at 5 years. The 5-year progression free survival was estimated using the Kaplan Meier method.
Measured: 5 years from registration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startApr 2002
- Primary completionApr 2012
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Adult Acute Lymphoblastic Leukemia in RemissionStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Meir Wetzler, Principal investigator, Cancer and Leukemia Group B
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00039377
- Sponsor's protocol ID
- NCI-2009-00436
- Other IDs
- NCI-2009-00436, CDR0000069378, CALGB 10001/SWOG C10001, CALGB-10001, U10CA031946
- Status last verified
- Jun 2014
- First submitted
- 6 Jun 2002
- Last updated
- 24 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wetzler M, Watson D, Stock W, Koval G, Mulkey FA, Hoke EE, McCarty JM, Blum WG, Powell BL, Marcucci G, Bloomfield CD, Linker CA, Larson RA. Autologous transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB Study 10001 (Alliance). Haematologica. 2014 Jan;99(1):111-5. doi: 10.3324/haematol.2013.085811. Epub 2013 Sep 27.
PubMed 24077846Mims AS, Kohlschmidt J, Borate U, Blachly JS, Orwick S, Eisfeld AK, Papaioannou D, Nicolet D, Mromicronzek K, Stein E, Bhatnagar B, Stone RM, Kolitz JE, Wang ES, Powell BL, Burd A, Levine RL, Druker BJ, Bloomfield CD, Byrd JC. A precision medicine classification for treatment of acute myeloid leukemia in older patients. J Hematol Oncol. 2021 Jun 23;14(1):96. doi: 10.1186/s13045-021-01110-5.
PubMed 34162404
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Sequential Chemotherapy, Imatinib Mesylate (Gleevec, STI571) (NSC # 716051), and Transplantation for Adults With Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia by the CALGB and SWOG
- ClinicalTrials.gov ID
- NCT00039377
- Acronym / sponsor ID
- NCI-2009-00436
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 2002
- Primary completion
- Apr 2012 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 18 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation works in treating patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Giving imatinib mesylate together with chemotherapy and peripheral stem cell transplantation may be an effective treatment for acute lymphoblastic leukemia.
Detailed description
PRIMARY OBJECTIVES:
- Determine the activity of imatinib mesylate (Gleevec) to prolong disease-free survival (DFS) and overall survival in acute lymphoblastic leukemia (ALL) patients with t(9;22).
II. Determine the ability of imatinib mesylate (Gleevec) to produce or maintain a BCR-ABL-negative status, as judged by real-time-polymerase chain reaction (RT-PCR) following sequential chemotherapy, imatinib mesylate (Gleevec) and transplantation.
III. Determine the feasibility of collecting adequate peripheral blood stem cells for autologous transplantation following imatinib mesylate (Gleevec) therapy.
IV. Study the safety and efficacy of autologous peripheral stem cell transplantation following therapy with imatinib mesylate (Gleevec).
- Study the safety and efficacy of allogeneic stem cell transplantation following therapy with imatinib mesylate (Gleevec).
VI. Study the safety and efficacy of imatinib mesylate (Gleevec) administered after allogeneic or autologous stem cell transplant.
OUTLINE:
COURSE I (remission induction): Patients receive 1 course of front-line induction therapy on a Cancer and Leukemia Group B (CALGB)/Southwest Oncology Group (SWOG) protocol prior to enrollment.
COURSE II (imatinib mesylate): Patients receive imatinib mesylate orally (PO) twice daily on days 1-28.
COURSE III (CNS prophylaxis): Within 7 days after completing course II, patients receive methotrexate intrathecally (IT), methotrexate intravenously (IV) over 3 hours, and vincristine sulfate IV on days 1, 8, and 15; methotrexate PO every 6 hours on days 1-2, 8-9, and 15-16; leucovorin calcium IV on days 2, 9, and 16; and leucovorin calcium PO every 6 hours on days 3, 4, 10, 11, 17, and 18.
COURSE IV (imatinib mesylate): 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.
COURSE Va (allogeneic PBSCT for patients with human leukocyte antigen [HLA]-matched sibling donor): 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 PO 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 subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.
COURSE Vb (autologous PBSCT for patients without HLA-matched sibling donor): 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 filgrastim SC beginning on day 14 and continuing until PBSC collection is complete. Patients receive imatinib mesylate PO 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 filgrastim SC beginning on day 0 and continuing until blood counts recover.
COURSE Vc (no transplantation for patients who are not transplant candidates): 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 filgrastim SC once or twice a day beginning on day 14 and continuing until blood counts recover.
COURSE VI: Patients receive imatinib mesylate PO once or twice daily beginning on day 30 post transplantation 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.
After completion of study treatment, patients are followed up monthly for 1 year, every 3 months for 2 years, every 6 months for 2 years, then yearly for 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (imatinib mesylate, chemotherapy, PBSCT) | Experimental | Drug: imatinib mesylate, Drug: methotrexate, Drug: vincristine sulfate, Drug: leucovorin calcium, Procedure: peripheral blood stem cell transplantation, Procedure: autologous hematopoietic stem cell transplantation, Procedure: allogeneic hematopoietic stem cell transplantation, Radiation: total-body irradiation, Drug: tacrolimus, Biological: filgrastim, Drug: etoposide, Drug: cyclophosphamide, Drug: cytarabine, Other: laboratory biomarker analysisSee Detailed Description. |
Who may qualify
- Ages
- 15 to 59 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Unequivocal histologic diagnosis of ALL
- Detection of the t(9;22)(q34;q11) or 3-way variant by metaphase cytogenetics or BCR-ABL positive by molecular analysis (RT-PCR or fluorescence in situ hybridization [FISH})
- Prior Therapy:
- No more than six weeks of prior imatinib mesylate during induction therapy before study enrollment
- Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control and contraception should continue for three months after the last dose of imatinib mesylate (Gleevec) to allow complete clearance of drug and its principle metabolites from the body; in women of childbearing potential, a pregnancy test will be required at study entry
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| imatinib mesylateAlso: CGP 57148, Gleevec, GlivecGiven PO | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| methotrexateAlso: amethopterin, Folex, methylaminopterin, MexateGiven IT and IV | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| vincristine sulfateAlso: leurocristine sulfate, VCR, Vincasar PFSGiven IV | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| leucovorin calciumAlso: CF, CFR, LVGiven IV and PO | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| peripheral blood stem cell transplantationAlso: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cellUndergo PBSCT | Procedure or surgery | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| autologous hematopoietic stem cell transplantationUndergo autologous PBSCT | Procedure or surgery | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| allogeneic hematopoietic stem cell transplantationUndergo allogeneic PBSCT | Procedure or surgery | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| total-body irradiationAlso: TBIUndergo TBI | Radiation | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| tacrolimusAlso: FK 506, PrografGiven IV or PO | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| filgrastimAlso: G-CSF, NeupogenGiven SC | Biological | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| etoposideAlso: EPEG, VP-16, VP-16-213Given IV | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| cyclophosphamideAlso: CPM, CTX, Cytoxan, EndoxanGiven IV | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| cytarabineAlso: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-UGiven IV | Drug | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (imatinib mesylate, chemotherapy, PBSCT) |
Primary outcome
Disease Free Survival
Time frame: Duration of treatment (up to 10 years)
Disease-free survival (DFS) was measured as the interval from achievement of complete remission (CR) until relapse or death, regardless of cause; patients alive and in CR were censored at last follow-up. DFS was estimated using the Kaplan Meier method. A complete remission (CR) was defined as recovery of morphologically normal bone marrow and blood counts (i.e., neutrophils >= 1.5 x 10^9/L and platelets > 100 x 10^9/L) and no circulating leukemic blasts or evidence of extramedullary leukemia and persisting for at least one month.
4 secondary outcomes
Overall Survival
Time frame: Duration of study (up to 10 years)
Number of Participants Who Achieved a BCR-ABL Response at 12 Months
Time frame: 12 months
5 Year Disease-free Survival for Autologous & Allogeneic Transplant Groups
Time frame: 5 years from CR
5 Year Overall Survival for Autologous & Allogeneic Transplant Groups
Time frame: 5 years from registration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24077846Wetzler M, Watson D, Stock W, Koval G, Mulkey FA, Hoke EE, McCarty JM, Blum WG, Powell BL, Marcucci G, Bloomfield CD, Linker CA, Larson RA. Autologous transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB Study 10001 (Alliance). Haematologica. 2014 Jan;99(1):111-5. doi: 10.3324/haematol.2013.085811. Epub 2013 Sep 27.
- Derived from this study: PubMed 34162404Mims AS, Kohlschmidt J, Borate U, Blachly JS, Orwick S, Eisfeld AK, Papaioannou D, Nicolet D, Mromicronzek K, Stein E, Bhatnagar B, Stone RM, Kolitz JE, Wang ES, Powell BL, Burd A, Levine RL, Druker BJ, Bloomfield CD, Byrd JC. A precision medicine classification for treatment of acute myeloid leukemia in older patients. J Hematol Oncol. 2021 Jun 23;14(1):96. doi: 10.1186/s13045-021-01110-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Meir Wetzler principal investigator
Cancer and Leukemia Group B
97 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imatinib mesylate, methotrexate and vincristine sulfate in people with Adult Acute Lymphoblastic Leukemia in Remission, run by National Cancer Institute (NCI) at 97 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 97 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease Free Survival (time frame: Duration of treatment (up to 10 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00039377, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2014.