Fludarabine and Radiation Therapy in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Chronic Phase or Accelerated Phase Chronic Myelogenous Leukemia

NCT00110058 | Completed Phase 2

• 3 other identifiers: 1954.00FHCRC-1954.00CDR0000423314
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops 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) or interferon alfa 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 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine together with radiation therapy works in treating patients who are undergoing donor stem cell transplant for chronic phase or accelerated phase chronic myelogenous leukemia.

Conditions

Leukemia

Keywords

accelerated phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; Philadelphia chromosome positive chronic myelogenous leukemia; relapsing chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

Secondary Outcomes (6)

• Rate of complete molecular response

• Late nonrelapse mortality

• Incidence and severity of graft-vs-host disease (GVHD)

• Incidence of serious infections

• Myelosuppression

Interventions

recombinant interferon alfa BIOLOGICAL

therapeutic allogeneic lymphocytes BIOLOGICAL

cyclosporine DRUG

fludarabine phosphate DRUG

imatinib mesylate DRUG

mycophenolate mofetil DRUG

peripheral blood stem cell transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia, meeting 1 of the following criteria: * Chronic phase * Ph+ by cytogenetics or fluorescent in situ hybridization (FISH) assay * Accelerated phase, meeting any of the following criteria: * More than 10% but \< 30% myeloblasts and promyelocytes in marrow or peripheral blood * Any additional clonal cytogenetic abnormalities * Increasing splenomegaly * Extramedullary tumor * WBC, platelet count, or hematocrit perturbations not controlled by therapy with hydroxyurea, interferon, or imatinib mesylate * Persistent unexplained fever or bone pain * Less than 5% blasts in the marrow at time of transplantation * Not eligible for OR refused conventional myeloablative allogeneic stem cell transplantation * Failed OR suboptimal response to prior imatinib mesylate, as defined by 1 of the following: * Absence of complete hematologic response after \> 3 months of treatment with imatinib mesylate * Absence of cytogenetic response, as defined by 1 of the following: * Absence of any cytogenetic response (\< 95% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 6 months of treatment with imatinib mesylate * Absence of major cytogenetic response (\< 35% Ph+ or BCR/ABL+ cells by cytogenetic or FISH analysis, respectively) after 1 year of treatment with imatinib mesylate * Absence of complete cytogenetic response (no Ph+ cells by cytogenetic analysis OR BCR/ABL+ cells within normal limits by FISH analysis) after 18 months of treatment with imatinib mesylate * Hematologic evidence of disease progression * Cytogenetic evidence of disease progression * Increase in Ph+ cells or BCR/ABL+ cells by \> 20% with at least 1 month between sequential testing * Molecular evidence of disease progression * More than 10-fold increase in BCR/ABL mRNA levels by quantitative polymerase chain reaction (Q-PCR) with at least 1 month between 2 sequential tests * Experienced adverse events during treatment with imatinib mesylate that precluded further administration of the drug * No CNS disease refractory to intrathecal chemotherapy * HLA identical related donor available * Phenotypically matched at HLA-A, -B, -C, DRQ1, and DBQ1 * No presence of circulating leukemic blasts by standard pathology PATIENT CHARACTERISTICS: Age * Any age Performance status * Karnofsky 70-100% OR * Lansky 70-100% Life expectancy * Not specified Hematopoietic * See Disease Characteristics Hepatic * No fulminant liver failure * No cirrhosis of the liver with evidence of portal hypertension or bridging fibrosis * No alcoholic hepatitis * No esophageal varices * No history of bleeding esophageal varices * No hepatic encephalopathy * No uncorrectable hepatic synthetic dysfunction evidenced by prolongation of PT * No ascites related to portal hypertension * No bacterial or fungal liver abscess * No biliary obstruction * No chronic viral hepatitis AND bilirubin \> 3 mg/dL * No symptomatic biliary disease Renal * Renal failure allowed Cardiovascular * No symptomatic coronary artery disease * Ejection fraction ≥ 35% * No other cardiac failure requiring therapy * No poorly controlled hypertension (blood pressure ≥ 150/90 mm Hg) on standard medication Pulmonary * DLCO ≥ 30% * Total lung capacity ≥ 30% * FEV\_1 ≥ 30% * No requirement for continuous supplementary oxygen * No fungal pneumonia with radiological progression after treatment with amphotericin or mold-active azoles for \> 1 month Other * Not pregnant or nursing * Fertile patients must use effective barrier contraception during and for 12 months after completion of study treatment * HIV negative * No other disease that severely limits life expectancy * No other active malignancy except localized nonmelanoma skin cancer * No nonhematologic malignancy within the past 5 years that is currently in complete remission and has a \> 20% risk of disease recurrence except for nonmelanoma skin cancer * No systemic uncontrolled infection * No active bacterial or fungal infection unresponsive to medical therapy PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics Chemotherapy * See Disease Characteristics Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified Other * At least 48 hours since prior imatinib mesylate

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (3)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Interferon-alpha; Cyclosporine; fludarabine phosphate; Imatinib Mesylate; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; 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

Study Officials

• Brenda Sandmaier, MD

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 3, 2005
• First Posted: May 4, 2005
• Study Start: February 1, 2005
• Study Completion: July 1, 2006
• Last Updated: November 17, 2011

Record last verified: 2011-11

Locations

US (3)