Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Allo-HSCT in Hematological Malignancies

NCT ID: NCT00544466

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2025-12-16

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.

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.

II. 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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

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

melphalan

Intervention Type: DRUG

140 mg/m2 day -2 prior to transplant

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Cells infused on Day 0 of transplant regimen

intensity-modulated radiation therapy

Intervention Type: RADIATION

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

Interventions

fludarabine phosphate

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

Intervention Type: DRUG

melphalan

140 mg/m2 day -2 prior to transplant

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Cells infused on Day 0 of transplant regimen

Intervention Type: PROCEDURE

intensity-modulated radiation therapy

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

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 7 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Rosenthal, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-04199

Identifier Type: -

Identifier Source: secondary_id

CDR0000570241

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2010-00355

Identifier Type: REGISTRY

Identifier Source: secondary_id

04199

Identifier Type: -

Identifier Source: org_study_id