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NCT00036738 · REGISTRY CONDITION SEARCH

Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2020-01-29

This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Relapse Free Survival

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outcome · POSTED

Leukemia-free Survival

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outcome · POSTED

Overall Survival

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outcome · POSTED

Transplant-related Mortality

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outcome · POSTED

Transplant-related Mortality

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * Patients =\< 12 years of age must be approved by Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) in advance * Patients with a history of Ph+ ALL or CML-BC who, after receiving imatinib mesylate, (or either dasatinib or nilotinib) have \< 15% blasts on morphologic marrow evaluation; patients with no detectable Ph+ ALL by morphologic or molecular assays (complete remission) will be accepted * An appropriately human leukocyte antigen (HLA) matched related or unrelated donor must be prospectively identified who will be available to donate filgrastim (G-CSF) mobilized stem cells * RELATED DONOR: * Related donor who is HLA genotypically identical at least at one haplotype and may be genotypically or phenotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1; * Donor must consent to G-CSR administration and leukapheresis; * Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) * HLA-MATCHED UNRELATED DONOR: * FHCRC matching allowed will be grades 1.0 to 2.1; unrelated donors who are prospectively matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing * A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before HCT; if the PRA shows \>10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results * Patient and donor pairs homozygous at a mismatched allele in the graft rejection vector are considered a two-allele mismatch, i.e., the patient is A\*0101 and the donor is A\*0102, and this type of mismatch is not allowed * Only G-CSF mobilized PBSC only will be permitted as a HSC source on this protocol Exclusion Criteria: * Central nervous system (CNS) involvement with leukemia refractory to intrathecal chemotherapy; prior to HSCT (all patients must receive a diagnostic lumbar puncture (LP) with intrathecal (IT) chemotherapy as per standard practice) * Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment * Patients with active non-hematologic malignancies (except non-melanoma skin cancers); this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy * Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a \> 20% risk of disease recurrence; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy * Females who are pregnant or breastfeeding * Patients who are human immunodeficiency virus (HIV)-positive * Patients with poorly controlled hypertension despite multiple antihypertensives * Adults: Karnofsky score \< 60 * Pediatrics: Lansky play-performance score \< 40 * Patients with cardiac ejection fraction \< 35% (or, if unable to obtain ejection fraction, shortening fraction of \< 26%); ejection fraction is required if age \> 50 years or there is a history of anthracycline exposure or history of cardiac disease; patients with a shortening fraction \< 26% may be enrolled if approved by a cardiologist * Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 30% * Total lung capacity (TLC) \< 30% * Forced expiratory volume in one second (FEV1) \< 30% and/or receiving supplementary continuous oxygen; the FHCRC PI of the study must approve enrollment of all patients with pulmonary nodules * Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, or symptomatic biliary disease * Creatinine levels more than 2.2 X's the upper limit of normal (ULN) at the laboratory where the analysis was performed * Patients with active bacterial or fungal infections unresponsive to medical therapy * For patients receiving dasatinib or nilotinib, baseline corrected QT interval (QTc) (Fridericia's method) prolongation greater than 500 msec * RELATED DONORS: * Identical twin * Infection with HIV * Inability to achieve adequate venous access * Known allergy to G-CSF * Current serious system illness * Bone marrow (BM) donors * HLA-MATCHED UNRELATED DONORS: * BM donors * Donors who are HIV-positive and/or, medical conditions that would result in increased risk for G-CSF mobilization and harvest of PBSC
healthy Volunteers
false
maximum Age
70 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Detailed Description
    intervention Names
    1. Drug: Cyclosporine
    2. Drug: Dasatinib
    3. Drug: Fludarabine Phosphate
    4. Drug: Imatinib Mesylate
    5. Drug: Mycophenolate Mofetil
    6. Drug: Nilotinib
    7. Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    8. Procedure: Peripheral Blood Stem Cell Transplantation
    9. Biological: Therapeutic Allogeneic Lymphocytes
    10. Radiation: Total-Body Irradiation
    label
    Treatment (allogeneic nonmyeloablative HSCT)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given IV or PO
    name
    Cyclosporine
    other Names
    1. 27-400
    2. Ciclosporin
    3. CsA
    4. Cyclosporin
    5. Cyclosporin A
    6. Gengraf
    7. Neoral
    8. OL 27-400
    9. Sandimmun
    10. Sandimmune
    11. SangCya
    type
    DRUG
  2. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given PO
    name
    Dasatinib
    other Names
    1. BMS-354825
    2. Sprycel
    type
    DRUG
  3. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given IV
    name
    Fludarabine Phosphate
    other Names
    1. 2-F-ara-AMP
    2. 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    3. Beneflur
    4. Fludara
    5. SH T 586
    type
    DRUG
  4. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given PO
    name
    Imatinib Mesylate
    other Names
    1. CGP 57148
    2. CGP57148B
    3. Gleevec
    4. Glivec
    5. STI 571
    6. STI-571
    7. STI571
    type
    DRUG
  5. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given PO
    name
    Mycophenolate Mofetil
    other Names
    1. Cellcept
    2. MMF
    type
    DRUG
  6. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given PO
    name
    Nilotinib
    other Names
    1. AMN 107
    2. Tasigna
    type
    DRUG
  7. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Undergo nonmyeloablative allogeneic PBSC transplantation
    name
    Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    other Names
    1. Non-myeloablative allogeneic transplant
    2. Nonmyeloablative Stem Cell Transplantation
    3. NST
    type
    PROCEDURE
  8. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Undergo allogeneic PBSC transplantation
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. PBSCT
    3. Peripheral Blood Progenitor Cell Transplantation
    4. Peripheral Stem Cell Support
    5. Peripheral Stem Cell Transplant
    6. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
  9. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Given IV
    name
    Therapeutic Allogeneic Lymphocytes
    other Names
    1. Allogeneic Lymphocytes
    type
    BIOLOGICAL
  10. arm Group Labels
    1. Treatment (allogeneic nonmyeloablative HSCT)
    description
    Undergo TBI
    name
    Total-Body Irradiation
    other Names
    1. Total Body Irradiation
    2. Whole-Body Irradiation
    type
    RADIATION
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
28
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Number of patients with relapsed disease within 1 Year post-transplant. Relapse is defined as the detection of \> 5% blasts after a documented complete remission.
    measure
    Relapse Free Survival
    time Frame
    Assessed up to 1 year
secondary Outcomes
  1. description
    Number of patients surviving in CR up to five years post-transplant.
    measure
    Leukemia-free Survival
    time Frame
    Assessed up to 5 years
  2. description
    Number of patients surviving up to five years post-transplant.
    measure
    Overall Survival
    time Frame
    Assessed up to 5 years
  3. description
    Number of patients with TRM within 100 days post-transplant.
    measure
    Transplant-related Mortality
    time Frame
    At day 100
  4. description
    Number of patients with TRM within one year post-transplant.
    measure
    Transplant-related Mortality
    time Frame
    At 1 year
Full study description
brief Summary
This phase II trial is studying how well fludarabine phosphate and total-body irradiation followed by donor peripheral blood stem cell transplant work in treating patients with acute lymphoblastic leukemia or chronic myelogenous leukemia that has responded to previous treatment with imatinib mesylate, dasatinib, or nilotinib. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.
detailed Description
PRIMARY OBJECTIVES: I. To determine whether the rate of leukemia relapse can be decreased for patients with chronic myelogenous leukemia in blast crisis (CML-BC) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) responsive to imatinib mesylate (or either dasatinib or nilotinib for patients who have imatinib-resistant disease or who are intolerant of imatinib) followed by nonmyeloablative hematopoietic stem cell transplantation (HSCT) compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy. II. To determine whether the rate of transplantation-related mortality (TRM) can be decreased for patients with CML-BC and Ph+ ALL responsive to imatinib mesylate (or dasatinib or nilotinib) followed by nonmyeloablative HSCT compared to historical controls given high-dose conventional allogeneic HSCT or chemotherapy. SECONDARY OBJECTIVES: I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with mixed or full donor chimerism as preemptive therapy to eliminate minimal residual disease. OUTLINE: INDUCTION THERAPY: Patients continue to receive imatinib mesylate orally (PO), dasatinib PO, or nilotinib PO once or twice daily until day -2 and resume on day 14 or when blood counts recover after peripheral blood stem cell (PBSC) transplantation. NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine intravenously (IV) on days -4 to -2; and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSC transplantation on day 0. GRAFT-VERSUS-HOST-DISEASE (GVHD) PROPHYLAXIS: Patients receive mycophenolate mofetil (MMF) PO every 12 hours on days 0-27 (related donor recipients) or every 8 hours on days 0-96 with taper on day 40 (unrelated donor recipients). Patients also receive cyclosporine IV or PO every 12 hours on days -3 to 56, followed by taper on days 57-180 (related donor recipients) or on days -3 to 100, followed by taper on days 101-177 (unrelated donor recipients). DONOR LYMPHOCYTE INFUSION: Patients with persistent disease and no GVHD after stopping GVHD prophylaxis receive donor lymphocyte infusion IV over 30 minutes once every 28 days for 3 doses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed up periodically for 2 years and then annually thereafter for 5 years.
Source references
references
  1. citation
    Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
    pmid
    32499241
    type
    DERIVED
  2. citation
    Ram R, Storb R, Sandmaier BM, Maloney DG, Woolfrey A, Flowers ME, Maris MB, Laport GG, Chauncey TR, Lange T, Langston AA, Storer B, Georges GE. Non-myeloablative conditioning with allogeneic hematopoietic cell transplantation for the treatment of high-risk acute lymphoblastic leukemia. Haematologica. 2011 Aug;96(8):1113-20. doi: 10.3324/haematol.2011.040261. Epub 2011 Apr 20.
    pmid
    21508120
    type
    DERIVED
Source notices and limitations
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    Preserved source evidence · Not medical advice