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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00800150
• Other study ID #: 08076
• Secondary ID: P30CA033572CHNMC
• Status: Terminated
• Phase: Phase 1
• First received: November 27, 2008
• Last updated: June 3, 2015
• Start date: November 2008
• Est. completion date: October 2010

Study information

• Verified date: June 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Neoplasms
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Drug:
• fludarabine phosphate

• melphalan

Procedure:
• nonmyeloablative allogeneic hematopoietic stem cell transplantation

Radiation:
• intensity-modulated radiation therapy

• tomotherapy

• total marrow irradiation

• total nodal irradiation

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy			No
Primary	Toxicity			Yes
Secondary	Frequency of clinical response			No
Secondary	Frequency of primary and secondary engraftment failure			No
Secondary	Time to neutrophil and platelet engraftment			No
Secondary	Incidence of acute and chronic graft-versus-host disease			No
Secondary	Overall survival			No
Secondary	Progression-free survival			No