- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00800150
Total Marrow and Total Lymph Node Irradiation, Fludarabine, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Hematological Cancer That Has Not Responded to Treatment
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
RATIONALE: Giving total marrow and total lymph node irradiation together with low doses of chemotherapy before a donor 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 cells and help destroy any remaining cancer cells (graft-versus-tumor effect).
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow and total lymph node irradiation when given together with fludarabine and melphalan followed by donor stem cell transplant in treating patients with advanced hematological cancer that has not responded to treatment.
Study Overview
Status
Conditions
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Duarte, California, United States, 91010-3000
- City of Hope Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Toxicity
|
Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy
|
Secondary Outcome Measures
Outcome Measure |
---|
Progression-free survival
|
Overall survival
|
Frequency of clinical response
|
Frequency of primary and secondary engraftment failure
|
Time to neutrophil and platelet engraftment
|
Incidence of acute and chronic graft-versus-host disease
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- primary myelofibrosis
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult Burkitt lymphoma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- 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)
- secondary acute myeloid leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- Waldenstrom macroglobulinemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- stage II multiple myeloma
- stage III multiple myeloma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent mantle cell lymphoma
- primary central nervous system non-Hodgkin lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- intraocular lymphoma
- angioimmunoblastic T-cell lymphoma
- anaplastic large cell lymphoma
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- adult grade III lymphomatoid granulomatosis
- adult nasal type extranodal NK/T-cell lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- cutaneous B-cell non-Hodgkin lymphoma
- refractory multiple myeloma
- recurrent adult acute lymphoblastic leukemia
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Precancerous Conditions
- Neoplasms
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Leukemia
- Preleukemia
- Plasmacytoma
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Melphalan
- Fludarabine
- Fludarabine phosphate
Other Study ID Numbers
- 08076
- P30CA033572 (U.S. NIH Grant/Contract)
- CHNMC-08076
- CDR0000626148 (REGISTRY: NCI PDQ)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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