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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Terminated

CT.gov ID

NCT00800150

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: fludarabine phosphate Drug: melphalan Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Radiation: intensity-modulated radiation therapy Radiation: tomotherapy Radiation: total marrow irradiation Radiation: total nodal irradiation	Phase 1

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

After completion of study treatment, patients are followed periodically.

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2008

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy []
Toxicity []

Secondary Outcome Measures

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 []
Overall survival []
Progression-free survival []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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