Clinical trial NCT00544466: Helical Tomotherapy, Fludarabine Phosphate, and Melphalan Followed By Allo-HSCT in Hematological Malignancies
Official title: Allogeneic Stem Cell Transplant With a Novel Conditioning Therapy Using Helical Tomotherapy, Melphalan, and Fludarabine in Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-16
Enrollment: 75
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Grade 3 and Above Toxicities of Helical Tomotherapy (HT) in Combination With Fludarabine and Melphalan Followed by Allogeneic Stem Cell Transplantation.
timeFrame: 100 days post treatment
Secondary outcomes:
measure: Overall Survival on Day 180 Days Post-transplant
timeFrame: Up to 180 days post-transplant
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Joseph Rosenthal, MD
role: PRINCIPAL_INVESTIGATOR
References: