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

NCT00544466 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 5 other identifiers: 04199P30CA033572CHNMC-04199CDR0000570241NCI-2010-00355
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

acute myeloid leukemia with multilineage dysplasia following myelodysplastic syndrome; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with del(5q); 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); untreated adult acute myeloid leukemia; recurrent adult acute myeloid leukemia; childhood acute myeloid leukemia in remission; recurrent childhood acute myeloid leukemia; untreated childhood acute myeloid leukemia and other myeloid malignancies; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary acute myeloid leukemia; childhood acute lymphoblastic leukemia in remission; recurrent adult acute lymphoblastic leukemia; recurrent childhood acute lymphoblastic leukemia; untreated adult acute lymphoblastic leukemia; untreated childhood acute lymphoblastic leukemia; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Number of Grade 3 and Above Toxicities of Helical Tomotherapy (HT) in Combination With Fludarabine and Melphalan Followed by Allogeneic Stem Cell Transplantation.

  Toxicities (adverse events) were evaluated using the modified Bearman Scale and the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

  100 days post treatment

Secondary Outcomes (1)

• Overall Survival on Day 180 Days Post-transplant

  Up to 180 days post-transplant

Study Arms (1)

Treatment (enzyme inhibitor, radiation therapy, transplant)

EXPERIMENTAL

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; Drug: melphalan; Procedure: allogeneic hematopoietic stem cell transplantation; Radiation: intensity-modulated radiation therapy

Interventions

fludarabine phosphate DRUG

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

Treatment (enzyme inhibitor, radiation therapy, transplant)

melphalan DRUG

140 mg/m2 day -2 prior to transplant

Treatment (enzyme inhibitor, radiation therapy, transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Cells infused on Day 0 of transplant regimen

Treatment (enzyme inhibitor, radiation therapy, transplant)

intensity-modulated radiation therapy RADIATION

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

Treatment (enzyme inhibitor, radiation therapy, transplant)

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Congenital Abnormalities; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

fludarabine phosphate; Melphalan; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Results Point of Contact

• Title: Dr. Jeffrey Wong, MD
• Organization: City of Hope Medical Center

JWong@coh.org

6263598111

Study Officials

• Joseph Rosenthal, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2007
• First Posted: October 16, 2007
• Study Start: July 31, 2006
• Primary Completion: August 1, 2013
• Study Completion (Estimated): December 2, 2026
• Last Updated: February 19, 2026
• Results First Posted: May 10, 2023

Record last verified: 2026-02

Locations

US (1)