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

NCT00036738 | Completed Phase 2 Results DMC

• 4 other identifiers: 1581.00NCI-2010-00131P01CA078902P30CA015704
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

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.

Conditions

Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Blastic Phase; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase of Disease; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Disease

Outcome Measures

Primary Outcomes (1)

• Relapse Free Survival

  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.

  Assessed up to 1 year

Secondary Outcomes (4)

• Leukemia-free Survival

  Assessed up to 5 years

• Overall Survival

  Assessed up to 5 years

• Transplant-related Mortality

  At day 100

• Transplant-related Mortality

  At 1 year

Study Arms (1)

Treatment (allogeneic nonmyeloablative HSCT)

EXPERIMENTAL

See Detailed Description

Drug: Cyclosporine; Drug: Dasatinib; Drug: Fludarabine Phosphate; Drug: Imatinib Mesylate; Drug: Mycophenolate Mofetil; Drug: Nilotinib; Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Biological: Therapeutic Allogeneic Lymphocytes; Radiation: Total-Body Irradiation

Interventions

Cyclosporine DRUG

Given IV or PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (allogeneic nonmyeloablative HSCT)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel

Treatment (allogeneic nonmyeloablative HSCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (allogeneic nonmyeloablative HSCT)

Imatinib Mesylate DRUG

Given PO

Also known as: CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571

Treatment (allogeneic nonmyeloablative HSCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (allogeneic nonmyeloablative HSCT)

Nilotinib DRUG

Given PO

Also known as: AMN 107, Tasigna

Treatment (allogeneic nonmyeloablative HSCT)

Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo nonmyeloablative allogeneic PBSC transplantation

Also known as: Non-myeloablative allogeneic transplant, Nonmyeloablative Stem Cell Transplantation, NST

Treatment (allogeneic nonmyeloablative HSCT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSC transplantation

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (allogeneic nonmyeloablative HSCT)

Therapeutic Allogeneic Lymphocytes BIOLOGICAL

Given IV

Also known as: Allogeneic Lymphocytes

Treatment (allogeneic nonmyeloablative HSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation

Treatment (allogeneic nonmyeloablative HSCT)

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, 80218, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Blast Crisis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Interventions

Cyclosporine; Cyclosporins; Dasatinib; fludarabine phosphate; Imatinib Mesylate; Mycophenolic Acid; nilotinib; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Caproates; Acids, Acyclic; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. George Georges
• Organization: Fred Hutchinson Cancer Research Center

ggeorges@fredhutch.org

206-667-6886

Study Officials

• George Georges

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2002
• First Posted: January 27, 2003
• Study Start: July 13, 2001
• Primary Completion: July 1, 2014
• Study Completion: May 1, 2018
• Last Updated: January 29, 2020
• Results First Posted: August 22, 2017

Record last verified: 2019-12

Locations

US (3)