Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Sponsor

City of Hope Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00544466

Collaborator

National Cancer Institute (NCI) (NIH)

100

Enrollment

Location

Arm

196

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy drugs, such as fludarabine phosphate and melphalan, and HT before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving HT together with fludarabine phosphate and melphalan before a transplant may stop this from happening.

PURPOSE: This clinical trial studies helical tomotherapy (HT), fludarabine phosphate, and melphalan followed by donor stem cell transplant in treating patients with hematologic malignancies.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: fludarabine phosphate Drug: melphalan Procedure: allogeneic hematopoietic stem cell transplantation Radiation: intensity-modulated radiation therapy	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES: I. To assess the feasibility in terms of toxicity and safety of HT in combination with Fludarabine (fludarabine phosphate) and Melphalan as a preparative regimen for allogeneic stem cell transplantation in patients with Hematological Malignancies: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndromes (MDS).

SECONDARY OBJECTIVES: I. To evaluate within the confines of this pilot study, incidence of neutrophil and platelet engraftment, survival on day +180, the overall survival, and disease free survival in patients with Hematological Malignancies: ALL, AML, and MDS.

To evaluate incidence of primary and secondary engraftment failure, incidence of relapse, incidence of acute and chronic transplant related complications, including veno-occlusive disease of the liver (VOD), organ toxicity, secondary malignancies, including treatment-related myelodysplastic syndrome, and acute and chronic graft-versus-host disease (GVHD), as well as post-transplant chimerism.

OUTLINE: PREPARATIVE REGIMEN*: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3 and melphalan IV on day -2. Patients also undergo HT twice daily on days -7 to -4.

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: *Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.

After completion of study treatment, patients are followed up periodically for 2 years.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Stem Cell Transplant With a Novel Conditioning Therapy Using Helical Tomotherapy, Melphalan, and Fludarabine in Hematological Malignancies

Actual Study Start Date :

Jul 31, 2006

Anticipated Primary Completion Date :

Nov 29, 2022

Anticipated Study Completion Date :

Nov 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (enzyme inhibitor, radiation therapy, transplant) PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. Patients also undergo helical tomotherapy twice daily on days -7 to -4. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.	Drug: fludarabine phosphate 25 mg/m2 day -7 through day -3 prior to transplant Drug: melphalan 140 mg/m2 day -2 prior to transplant Procedure: allogeneic hematopoietic stem cell transplantation Cells infused on Day 0 of transplant regimen Radiation: intensity-modulated radiation therapy Each fraction is 150 cGy, 2 fractions each day on day -7 through day -4 prior to transplant

Arm

Intervention/Treatment

Experimental: Treatment (enzyme inhibitor, radiation therapy, transplant)

PREPARATIVE REGIMEN*: Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. Patients also undergo helical tomotherapy twice daily on days -7 to -4. TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0. NOTE: *Treatment begins 2 days earlier in patients receive tacrolimus and/or sirolimus for GVHD prophylaxis.

Drug: fludarabine phosphate

25 mg/m2 day -7 through day -3 prior to transplant

Drug: melphalan

140 mg/m2 day -2 prior to transplant

Procedure: allogeneic hematopoietic stem cell transplantation

Cells infused on Day 0 of transplant regimen

Radiation: intensity-modulated radiation therapy

Each fraction is 150 cGy, 2 fractions each day on day -7 through day -4 prior to transplant

Outcome Measures

Primary Outcome Measures

Toxicity of helical tomotherapy (HT) in combination with fludarabine and melphalan followed by allogeneic stem cell transplantation [100 days post treatment]
Descriptive statistics will be used to summarize data outcomes. The type and grade of toxicities during therapy will be tabulated. Toxicities will be evaluated using the modified Bearman Scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Secondary Outcome Measures

Incidence of neutrophil and platelet engraftment [100 days post treatment]
Incidence of relapse [2 years post treatment]
Incidence of acute and chronic transplant-related complications, including acute and chronic graft-vs-host disease [2 years post treatment]
Secondary malignancy, including treatment-related myelodysplastic syndrome [2 years post treatment]
Overall survival on day 180 days post-transplant [180 days post-transplant]
Disease-free survival 180 days post-transplant [180 days post-transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Recipient, or recipient's parents, or recipient's legal guardians must have signed a voluntary, informed consent in accordance with institutional and federal guidelines
Must have histopathologically confirmed diagnosis in one of the followed categories:
AML
MDS with intermediate or high-risk disease
ALL
Children and adults at any age with significant morbidity, as determined by the primary bone marrow transplant (BMT) doctor (MD), and approved by the principal investigator (PI)
Able to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session; for younger patients deep conscious sedation may be required
Performance status evaluated by Zubrod or Karnofsky (KPS) Performance Scales in patients > 16 years or Lanksy Performance Scale in children =< 16 years must have a score >= 70%
Adequate cardiac function: cardiac ejection fraction > 50% by multi gated acquisition scan (MUGA) scan and/or by echocardiogram
Adequate pulmonary function: adults (older than 16 years): diffusing capacity of carbon monoxide (DLCO) > 50%; for young children in whom pulmonary function tests (PFT) are not applicable: assessment by a pediatrician or pulmonary consult
Adequate renal function as demonstrated by: creatinine clearance or glomerular filtration rate (GFR) > 60 cc/min (24 hour urine collection)
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) =< 5.0 times the institutional upper limits of normal
Patients must have less than 15% peripheral blasts
Pre-treatment tests must have been preformed within 30 days prior to initiation of high-dose chemotherapy
No other medical and/or psychosocial problems, which in the opinion of the primary physician or principle investigator would place the patient at unacceptable risk from this regimen

Exclusion Criteria:

Patients with Acute Undifferentiated Leukemia (AUL), i.e. no lymphoid or myeloid markers
Previous radiation therapy to more than 20% of bone marrow containing areas, or to any area exceeding 2000 cGy
Patients with Fanconi Anemia
Major medical or psychiatric disorders that would seriously compromise patient tolerance of this regimen
Human immunodeficiency virus (HIV) infection
Evidence of Hepatitis B or C infection or evidence of cirrhosis
Uncontrolled viral, bacterial or fungal infection
Patients with recent (within 4 weeks) serious viral, fungal, or bacterial infection are excluded
Patients with radiographic changes indicating pulmonary disease, including but not limited to: pulmonary nodules, infiltrates, pleural effusion are excluded unless cleared by pulmonary biopsy showing no evidence for active pulmonary disease