Clinical trial NCT00008307: Combination Chemotherapy Followed by Donor Bone Marrow Transplant or Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer or Genetic Disorders
Official title: Non-Ablative Chemotherapeutic Conditioning Before Allogeneic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
stage I cutaneous T-cell non-Hodgkin lymphoma
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
refractory multiple myeloma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
stage I childhood lymphoblastic lymphoma
stage II childhood lymphoblastic lymphoma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
untreated adult acute lymphoblastic leukemia
untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
untreated childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
chronic myelogenous leukemia, BCR-ABL1 positive
Philadelphia chromosome negative chronic myelogenous leukemia
stage II childhood Hodgkin lymphoma
stage I childhood Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
stage I grade 1 follicular lymphoma
stage I grade 2 follicular lymphoma
stage I grade 3 follicular lymphoma
stage I adult diffuse small cleaved cell lymphoma
stage I adult diffuse mixed cell lymphoma
stage I adult diffuse large cell lymphoma
stage I adult immunoblastic large cell lymphoma
stage I adult lymphoblastic lymphoma
stage I adult Burkitt lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
stage I adult T-cell leukemia/lymphoma
stage II adult T-cell leukemia/lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
intraocular lymphoma
stage I childhood large cell lymphoma
stage II childhood large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
recurrent childhood large cell lymphoma
stage I mantle cell lymphoma
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II mantle cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
contiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage I mycosis fungoides/Sezary syndrome
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
childhood chronic myelogenous leukemia
contiguous stage II small lymphocytic lymphoma
contiguous stage II marginal zone lymphoma
noncontiguous stage II small lymphocytic lymphoma
noncontiguous stage II marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage I marginal zone lymphoma
stage I small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage III marginal zone lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with t(15;17)(q22;q12)
childhood myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 52
Sex: ALL
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy drugs, such as fludarabine and melphalan, before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal 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.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy followed by donor bone marrow transplant or peripheral stem cell transplant works in treating patients with hematologic cancer or genetic disorders.

Detailed description: OBJECTIVES:

* Determine the hematopoietic recovery in patients with hematologic malignancies or genetic disorders treated with fludarabine and melphalan followed by allogeneic or syngeneic bone marrow or peripheral blood stem cell transplantation.
* Determine the chemotherapeutic toxicity of this regimen in these patients.
* Determine the relapse and survival of patients treated with this regimen.
* Determine the incidence of graft-versus-host disease in patients treated with this regimen.

OUTLINE: Patients receive fludarabine IV on days -6 to -2 and melphalan IV on days -3 and -2. Patients with a non-HLA-identical family member may also receive anti-thymocyte globulin on days -4 to -1. Patients undergo allogeneic or syngeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients receive graft-vs-host disease prophylaxis comprising mycophenolate mofetil twice daily beginning on day -3, methylprednisolone beginning on day 5 and continuing over 8 weeks, and cyclosporine IV or orally beginning on day -3 and continuing until at least 6 months post-transplantation.

Patients are followed at 1, 3, and 6 months, and then at 1 year post-transplantation.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study within 5-6 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Clinically and/or histologically confirmed hematologic malignancy or genetic disorder

  * Chronic myelogenous leukemia

    * Typical blood and marrow morphology
    * Presence of Philadelphia chromosome OR
    * Molecular evidence of bcr/abl rearrangement if Philadelphia chromosome-negative
  * Acute myeloid leukemia, acute lymphocytic leukemia, myelodysplasia, or lymphoma

    * High risk of relapse or progressive disease
    * Typical clinical features and morphology in blood, marrow, lymph node, or other tissue by cytochemistry, immunophenotyping, and/or chromosomal abnormalities
  * Multiple myeloma

    * Typical marrow morphology, radiographic findings, and paraprotein
  * Aplastic anemia

    * Typical marrow and blood findings
  * Genetic disorder including storage disease (e.g., adrenoleukodystrophy), hemoglobinopathies (e.g., thalassemia), or severe immunodeficiency
* Unwilling to undergo conventional high-dose chemoradiotherapeutic conditioning prior to allogeneic stem cell transplantation OR
* Presence of other medical disorder which precludes high-dose chemoradiotherapeutic conditioning (e.g., cardiac disease or infection)
* Syngeneic twin, HLA-identical, or 1 or 2 HLA antigen-mismatched family member or unrelated donor

PATIENT CHARACTERISTICS:

Age:

* 1 to 80

Performance status:

* Karnofsky 50-100%

Life expectancy:

* Not specified

Hematopoietic:

* Not specified

Hepatic:

* Not specified

Renal:

* Not specified

Other:

* No other serious medical or psychiatric illness that would preclude study compliance
* Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* See Disease Characteristics

Chemotherapy:

* See Disease Characteristics

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics

Surgery:

* Not specified

Primary outcomes:
measure: Hematopoietic recovery
measure: Incidence of graft-versus-host disease
Secondary outcomes:
measure: Chemotherapeutic toxicity
measure: Relapse and survival
Other outcomes:
Locations:
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University
state: New York
Study officials:
affiliation: Herbert Irving Comprehensive Cancer Center
name: David G. Savage, MD
role: STUDY_CHAIR
References: