Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen
16 Years
N/A
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen
OBJECTIVES:
Primary
- To determine the maximum tolerated dose of intensity-modulated total marrow and lymph
node irradiation (TMLI) using helical tomotherapy in combination with a
reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in
patients undergoing allogeneic hematopoietic stem cell transplantation for advanced,
relapsed or refractory hematological malignancies.
- To describe the toxicities of escalating doses of TMLI in these patients.
Secondary
- To describe the frequency of clinical response in patients treated with this regimen.
- To describe the frequency of primary and secondary engraftment failure in patients
treated with this regimen.
- To describe the time to neutrophil and platelet engraftment in patients treated with
this regimen.
- To describe the incidence of acute and chronic graft-versus-host disease in patients
treated with this regimen.
- To describe the overall survival of patients treated with this regimen.
- To describe the progression-free survival of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node
irradiation (TMLI).
- Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow,
major lymph node chains, spleen, and liver using helical tomotherapy twice daily on
days -6 to -3.
- Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on
days -6 to -2 and melphalan IV on day -1.
- Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day
0.
After completion of study treatment, patients are followed periodically.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histopathologically confirmed diagnosis of 1 of the following:
- Acute myeloid leukemia (AML)
- Myelodysplastic syndromes
- Intermediate- or high-risk disease
- Myelofibrosis
- Granulocytic sarcoma (chloroma)
- With or without bone marrow involvement
- Mixed lineage leukemia
- Induction therapy must have been directed predominantly against AML
- Acute lymphoblastic leukemia
- Non-Hodgkin lymphoma
- Multiple myeloma
- Relapsed or refractory disease with M3 marrow (marrow blasts > 25%), meeting 1 of the
following criteria:
- Persistent disease after an induction attempt
- Persistent initial disease after two induction attempts
- Relapse after one re-induction attempt (second relapse)
- Persistent disease after first relapse and initial re-induction attempt
- Not eligible for myeloablative allogeneic hematopoietic stem cell transplantation due
to age (> 50 years), organ insufficiency, or significant comorbidity
- Patients 16-50 years of age must meet ≥ 1 of the following criteria:
- Ejection fraction 50-60% by MUGA scan and/or echocardiogram
- DLCO 50-75% of predicted
- Creatinine clearance or GFR 60-80 mL/min
- Serum bilirubin ≤ 2.0 mg/dL
- SGOT and SGPT 1.5-5 times upper limit of normal
- No other medical and/or psychosocial problem that, in the opinion of the
primary physician or principal investigator, would place the patient at
unacceptable risk from study regimen
- No Fanconi anemia
- HLA-identical sibling OR matched unrelated donor available
PATIENT CHARACTERISTICS:
- Zubrod or Karnofsky performance status 70-100%
- Negative pregnancy test
- Able to lie supine in a full body cast for 30 minutes
- No HIV infection
- No evidence of active hepatitis B or C infection
- No evidence of cirrhosis
- No uncontrolled viral, bacterial, or fungal infection within the past 4 weeks
- No radiographic changes indicating pulmonary disease (e.g., pulmonary nodules,
infiltrates, or pleural effusion) unless cleared by pulmonary biopsy that shows no
evidence of active pulmonary disease
- No major medical or psychiatric disorder that would seriously compromise patient
tolerance of study regimen
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior radiation therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy
Safety Issue:
No
Principal Investigator
Joseph Rosenthal, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Beckman Research Institute
Authority:
United States: Institutional Review Board
Study ID:
08076
NCT ID:
NCT00800150
Start Date:
November 2008
Completion Date:
October 2010
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult T-cell leukemia/lymphoma
- secondary acute myeloid leukemia
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- adult grade III lymphomatoid granulomatosis
- adult nasal type extranodal NK/T-cell lymphoma
- anaplastic large cell lymphoma
- angioimmunoblastic T-cell lymphoma
- splenic marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- stage III adult Burkitt lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage III mycosis fungoides/Sezary syndrome
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III small lymphocytic lymphoma
- stage IV adult Burkitt lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- stage IV mycosis fungoides/Sezary syndrome
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- intraocular lymphoma
- primary central nervous system non-Hodgkin lymphoma
- primary myelofibrosis
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- cutaneous B-cell non-Hodgkin lymphoma
- Waldenstrom macroglobulinemia
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
