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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00544466
First received: October 13, 2007
Last updated: July 10, 2014
Last verified: July 2014
  Purpose

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 Intervention
Leukemia
Myelodysplastic Syndromes
Drug: fludarabine phosphate
Drug: melphalan
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: intensity-modulated radiation therapy

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Toxicity of helical tomotherapy (HT) in combination with fludarabine and melphalan followed by allogeneic stem cell transplantation [ Time Frame: 100 days post treatment ] [ Designated as safety issue: Yes ]
  • Safety [ Time Frame: 100 days post treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of neutrophil and platelet engraftment [ Time Frame: 100 days post treatment ] [ Designated as safety issue: No ]
  • Incidence of relapse [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Incidence of acute and chronic transplant-related complications, including acute and chronic graft-vs-host disease [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Secondary malignancy, including treatment-related myelodysplastic syndrome [ Time Frame: 2 years post treatment ] [ Designated as safety issue: No ]
  • Overall survival on day 180 days post-transplant [ Time Frame: 180 days post-transplant ] [ Designated as safety issue: No ]
  • Disease-free survival 180 days post-transplant [ Time Frame: 180 days post-transplant ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: November 2005
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544466

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Joseph Rosenthal, MD City of Hope Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00544466     History of Changes
Other Study ID Numbers: 04199, P30CA033572, CHNMC-04199, CDR0000570241, NCI-2010-00355
Study First Received: October 13, 2007
Last Updated: July 10, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
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

Additional relevant MeSH terms:
Neoplasms
Leukemia
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms by Site
Melphalan
Fludarabine
Fludarabine phosphate
Vidarabine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 27, 2014