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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


Phase 1
16 Years
N/A
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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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 CenterDuarte, California  91010