Total Marrow and Total Lymph Node Irradiation, Fludarabine, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Hematological Cancer That Has Not Responded to Treatment

This study has been terminated.
(Protocol objective could not be met. A new study with amended eligibility criteria will be developed.)
Sponsor:
Collaborator:
Information provided by:
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00800150
First received: November 27, 2008
Last updated: July 28, 2011
Last verified: July 2011
  Purpose

RATIONALE: Giving total marrow and total lymph node irradiation together with low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

PURPOSE: This phase I trial is studying the side effects and best dose of total marrow and total lymph node irradiation when given together with fludarabine and melphalan followed by donor stem cell transplant in treating patients with advanced hematological cancer that has not responded to treatment.


Condition Intervention Phase
Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Drug: fludarabine phosphate
Drug: melphalan
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Radiation: intensity-modulated radiation therapy
Radiation: tomotherapy
Radiation: total marrow irradiation
Radiation: total nodal irradiation
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Frequency of clinical response [ Designated as safety issue: No ]
  • Frequency of primary and secondary engraftment failure [ Designated as safety issue: No ]
  • Time to neutrophil and platelet engraftment [ Designated as safety issue: No ]
  • Incidence of acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: November 2008
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation (TMLI) using helical tomotherapy in combination with a reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in patients undergoing allogeneic hematopoietic stem cell transplantation for advanced, relapsed or refractory hematological malignancies.
  • To describe the toxicities of escalating doses of TMLI in these patients.

Secondary

  • To describe the frequency of clinical response in patients treated with this regimen.
  • To describe the frequency of primary and secondary engraftment failure in patients treated with this regimen.
  • To describe the time to neutrophil and platelet engraftment in patients treated with this regimen.
  • To describe the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
  • To describe the overall survival of patients treated with this regimen.
  • To describe the progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node irradiation (TMLI).

  • Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow, major lymph node chains, spleen, and liver using helical tomotherapy twice daily on days -6 to -3.
  • Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and melphalan IV on day -1.
  • Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.

After completion of study treatment, patients are followed periodically.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histopathologically confirmed diagnosis of 1 of the following:

    • Acute myeloid leukemia (AML)
    • Myelodysplastic syndromes

      • Intermediate- or high-risk disease
    • Myelofibrosis
    • Granulocytic sarcoma (chloroma)

      • With or without bone marrow involvement
    • Mixed lineage leukemia

      • Induction therapy must have been directed predominantly against AML
    • Acute lymphoblastic leukemia
    • Non-Hodgkin lymphoma
    • Multiple myeloma
  • Relapsed or refractory disease with M3 marrow (marrow blasts > 25%), meeting 1 of the following criteria:

    • Persistent disease after an induction attempt
    • Persistent initial disease after two induction attempts
    • Relapse after one re-induction attempt (second relapse)
    • Persistent disease after first relapse and initial re-induction attempt
  • Not eligible for myeloablative allogeneic hematopoietic stem cell transplantation due to age (> 50 years), organ insufficiency, or significant comorbidity

    • Patients 16-50 years of age must meet ≥ 1 of the following criteria:

      • Ejection fraction 50-60% by MUGA scan and/or echocardiogram
      • DLCO 50-75% of predicted
      • Creatinine clearance or GFR 60-80 mL/min
      • Serum bilirubin ≤ 2.0 mg/dL
      • SGOT and SGPT 1.5-5 times upper limit of normal
      • No other medical and/or psychosocial problem that, in the opinion of the primary physician or principal investigator, would place the patient at unacceptable risk from study regimen
  • No Fanconi anemia
  • HLA-identical sibling OR matched unrelated donor available

PATIENT CHARACTERISTICS:

  • Zubrod or Karnofsky performance status 70-100%
  • Negative pregnancy test
  • Able to lie supine in a full body cast for 30 minutes
  • No HIV infection
  • No evidence of active hepatitis B or C infection
  • No evidence of cirrhosis
  • No uncontrolled viral, bacterial, or fungal infection within the past 4 weeks
  • No radiographic changes indicating pulmonary disease (e.g., pulmonary nodules, infiltrates, or pleural effusion) unless cleared by pulmonary biopsy that shows no evidence of active pulmonary disease
  • No major medical or psychiatric disorder that would seriously compromise patient tolerance of study regimen

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior radiation therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00800150

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

No publications provided

Responsible Party: Joseph Rosenthal, City of Hope Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00800150     History of Changes
Other Study ID Numbers: 08076, P30CA033572, CHNMC-08076, CDR0000626148
Study First Received: November 27, 2008
Last Updated: July 28, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
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)
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
stage III adult Burkitt lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage III mycosis fungoides/Sezary syndrome
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III mantle cell lymphoma

Additional relevant MeSH terms:
Neoplasms
Leukemia
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Lymphoma, Large-Cell, Immunoblastic
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Bone Marrow Diseases
Precancerous Conditions
Melphalan
Fludarabine
Fludarabine monophosphate
Vidarabine

ClinicalTrials.gov processed this record on April 17, 2014