Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00006379

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

136

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have hematologic cancer or aplastic anemia.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases Precancerous/Nonmalignant Condition Small Intestine Cancer	Biological: anti-thymocyte globulin Biological: graft-versus-tumor induction therapy Drug: cyclophosphamide Drug: fludarabine phosphate Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Determine the rates of durable full donor hematologic engraftment in patients with high-risk hematologic malignancies or severe aplastic anemia treated with non-myeloablative conditioning using fludarabine, cyclophosphamide, and anti-thymocyte globulin followed by allogeneic peripheral blood stem cell transplantation.
Determine the acute and delayed toxic effects of this non-myeloablative conditioning regimen in this patient population.
Determine the event-free and overall survival of patients treated with this regimen.
Determine the incidence and severity of acute and chronic graft-versus-host disease in patients treated with this regimen.
Determine the rate and quality of immune reconstitution in patients treated with this regimen.
Determine the rate of disease relapse and incidence of post-transplantation lymphoproliferative disease in these patients.

OUTLINE: Patients are stratified according to disease category (malignant vs non-malignant) and graft source (unrelated vs HLA-matched sibling).

Beginning at least 4 weeks after conventional-dose chemotherapy, patients receive non-myeloablative conditioning comprising fludarabine IV over 30 minutes on days -8 to -4, cyclophosphamide IV over 2 hours on days -3 to -2, and anti-thymocyte globulin IV over at least 4 hours on days -2 and -1. Patients undergo filgrastim (G-CSF)-mobilized allogeneic peripheral blood stem cell transplantation on day 0.

Patients are followed weekly for 3 months, every 2 weeks for 3 months, monthly for 6 months, and then every 2 months thereafter.

PROJECTED ACCRUAL: A minimum of 30 patients will be accrued for this study within 4 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

58 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Purine-Analog-Containing Non-Myeloablative Allogeneic Stem Cell Transplantation for Treatment of Hematologic Malignancies and Severe Aplastic Anemia

Study Start Date :

Jun 1, 2000

Actual Primary Completion Date :

Jan 1, 2004

Actual Study Completion Date :

Oct 1, 2011

Outcome Measures

Primary Outcome Measures

Evaluation of Donor Engraftment [at 28 days]
Peripheral blood from the donor and patient is obtained for chimerism studies. The primary analysis will consist of estimating the graft failure proportions for each of the separate patient groups and calculating confidence intervals for these proportions. This analysis will be done conditional on patients surviving at least 28 days.

Secondary Outcome Measures

Stable donor hematopoietic chimerism [at day 100]
Number of Patients Transplanted More Than 100 Days Ago
Event free and overall survival [to progression/death]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically proven high-risk hematologic malignancy
Acute non-lymphocytic leukemia (ANLL) after induction failure, or in first complete remission (CR) with high-risk features, including any of the following:
Stem cell or biphenotypic classification (AML-M0)
Erythroleukemia (AML-M6)
Acute megakaryocytic leukemia (AML-M7)
Cytogenetic markers indicative of poor prognosis
Failure to achieve CR after standard induction therapy
Acute lymphocytic leukemia (ALL) or ANLL in relapse or second or subsequent remission
Chronic myelogenous leukemia (CML) in chronic or accelerated phase
Patients with CML in blast crisis are eligible after reinduction chemotherapy places them in chronic phase
High-risk ALL in first CR with high risk defined by presence of t(4;11), t(9;22) translocation, hyperleukocytosis (initial WBC greater than 30,000/mm^3), or failure to achieve CR by day 28 after standard induction
No T-cell ALL or t(8;14) positive B-cell ALL in first remission with hyperleukocytosis
Myelodysplastic syndrome by peripheral blood smear and bone marrow examination
Refractory to medical management OR
Cytogenetic abnormalities predictive of transformation into acute leukemia including 5q-, 7q-, monosomy 7, and trisomy 8 OR
Evidence of evolution to AML (e.g., refractory anemia with excess blasts (RAEB) or RAEB in transformation)
Multiple myeloma, non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation (SCT)
At least 3 months since prior autologous SCT
Hodgkin's lymphoma, NHL, or multiple myeloma beyond first CR or primary induction failures whose disease has demonstrated sensitivity to pre-transplantation cytoreduction (defined as greater than 50% reduction in tumor burden)
Mantle zone NHL allowed after induction therapy
Myeloproliferative disorder that is non-responsive to medical management and requires allografting, unless evidence of grade 3 or worse myelofibrosis on marrow biopsy OR
Histologically proven acquired severe aplastic anemia (SAA) that is recurrent or unresponsive after anti-thymocyte globulin and/or cyclosporine
SAA defined by at least 2 of the following conditions:
Granulocyte count less than 500/mm^3
Platelet count less than 20,000/mm^3
Absolute reticulocyte count less than 20,000/mm^3 after correction for hematocrit
Ineligible for full ablative conditioning due to any of the following conditions:
Prior extensive therapy (more than 2 salvage chemotherapy regimens and/or autologous transplantation)
Over age 55 OR
Under age 55 with comorbid disease (e.g., suboptimal cardiac, pulmonary, or renal function and/or prior life-threatening infection)
HLA-A, B, and DR phenotypically identical sibling donor OR
HLA-A, B, and DR identical genetically matched unrelated donor
No ANLL in first CR (less than 5% blasts in marrow) with translocations t(8;21) and inv(16) unless failed first-line induction therapy OR
No ANLL in first CR (less than 5% blasts in marrow) with translocations t(15;17) abnormality unless failed first-line induction therapy OR molecular evidence of persistent disease
No active CNS disease

PATIENT CHARACTERISTICS:

Age:

0 to 70

Performance status:

Zubrod 0-1
Karnofsky 80-100%

Life expectancy:

At least 3 months

Hematopoietic:

See Disease Characteristics

Hepatic:

ALT/AST no greater than 4 times normal
Bilirubin no greater than 2.0 mg/dL

Renal:

See Disease Characteristics
Creatinine clearance at least 50 mL/min

Cardiovascular:

See Disease Characteristics
Shortening fraction or ejection fraction at least 40% of normal for age by echocardiogram or radionuclide scan
No clinically significant comorbid illnesses (e.g., myocardial infarction or cerebrovascular accident)