Bone Marrow Transplantation in Treating Patients With Leukemia, Myelodysplasia, or Lymphoblastic Lymphoma

NCT ID: NCT00003187

Last Updated: 2010-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-05-31
• Study Completion Date: 2005-02-28

Brief Summary

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Eliminating the T cells from the donor cells before transplanting them may prevent this from happening.

PURPOSE: Randomized phase II/III trial to compare the effectiveness of conventional bone marrow transplantation with T cell-depleted bone marrow transplantation in treating patients who have leukemia, myelodysplasia, or lymphoblastic lymphoma.

Detailed Description

OBJECTIVES: I. Compare the disease free survival of patients with leukemia, myelodysplasia, or lymphoblastic lymphoma after treatment with conventional (non-T cell depleted) or T cell depleted unrelated donor bone marrow transplantation. II. Compare the incidence of primary and secondary graft failure, acute and chronic graft-vs-host disease, complications (infection, veno-occlusive disease, interstitial pneumonitis), and relapse in these patients after these treatments. III. Compare the incidence of other malignancies, lymphoproliferative disorders, and post-transplant myelodysplasia in these patients after these treatments.

OUTLINE: This is a randomized, multicenter study. Patients will be stratified according to institution. Patients are assigned to one of two treatment arms, one with conventional bone marrow transplantation (arm I) and one with T cell depletion of the bone marrow (arm II). Arm I: Patients receive cyclophosphamide on days -6 and -5. Total body irradiation (TBI) is administered on days -4 to 0, although this order may be reversed. Males with ALL receive a testicular boost of radiation therapy. Bone marrow is infused on day 0. Patients receive cyclosporine beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Arm II: T cell depletion is conducted by 2 different methods, according to the institution, and treatment varies depending on the method used. Method I is by T10B9 depletion and Method II is by counterflow elutriation depletion. Method I: Depending on the institution, some patients receive TBI on days -9 to -7 (before chemotherapy) (Course I) and some receive TBI on days -3 to -1 (after chemotherapy) (Course II). Course I also includes cytarabine IV on days -5 to -3, cyclophosphamide IV on days -2 and -1, and methylprednisolone IV on days -2 to 0 and 5-18. Bone marrow infusion is administered on day 0. Cyclosporine begins on day -1. Course II includes cytarabine IV on days -7 to -4 and cyclophosphamide on days -6 to -5. Methylprednisolone IV is administered on days -2 to 0 and 5-18. Bone marrow infusion is administered on day 0. Cyclosporine begins on day 0. Method II: Preparative therapy varies according to the disease category. Acute lymphoblastic leukemia: Patients undergo TBI on days -7 to -4. Males receive testicular boost on day -7, and all receive electron boost to anterior and posterior chest wall on days -5 and -4. Cyclophosphamide IV is administered on days -3 and -2. Bone marrow infusion is administered on day 0. Acute nonlymphocytic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome: Patients receive cyclophosphamide IV on days -7 and -6, followed by TBI on days -4 to -1. Bone marrow infusion is administered on day 0. Patients receive methylprednisolone IV every 12 hr on days -2,-1, and 5-19. Cyclosporine is administered from day -3 to day 180. All patients on both arms receive filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning on day 7 post-transplant. Patients are followed weekly for the first 14 weeks, at day 100, every 6 months for 2 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 560 patients will be accrued for this study within 4 years.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

methylprednisolone

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

in vitro-treated bone marrow transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Pathologically confirmed acute myeloid leukemia Not in first complete remission with translocations t(8;21) unless failed first line induction therapy Not in first complete remission with translocations t(15;17) or 16q abnormality unless: Failed first line induction therapy OR Molecular evidence of disease Pathologically confirmed acute lymphoblastic lymphoma (ALL) Not in first complete remission OR High risk ALL in first complete remission defined as: Hypodiploidy OR Pseudodiploidy with translocations t(9,22), t(4;11), or t(8;14) OR Elevated WBC at presentation Greater than 100,000/mm3 if 6-12 months old Greater than 50,000/mm3 if 10-20 years old Greater than 20,000/mm3 if 21 or over OR Failed to achieve complete remission after 4 weeks of induction therapy Pathologically confirmed chronic myelogenous leukemia (CML) not in blast crisis Pathologically confirmed undifferentiated leukemia or biphenotypic leukemia Pathologically confirmed juvenile CML with or without either 7q- or infantile monosomy 7 Leukocytosis with absolute monocytosis greater than 450 microliters AND Immature myeloid cells in peripheral blood circulation Less than 25% marrow blasts Myelodysplastic syndromes: Refractory anemia (RA) RA with ringed sideroblasts RA with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Pathologically confirmed stage IV lymphoblastic lymphoma No active CNS or skin leukemic involvement No consenting suitably HLA-matched related donor available Consenting unrelated donor available

PATIENT CHARACTERISTICS: Age: 55 and under Performance status: Karnofsky 70-100% OR Lansky 60-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 mg/dL SGOT less than 3 times upper limit of normal Renal: Creatinine within normal range OR Creatinine clearance greater than 60 mL/min Cardiovascular: Asymptomatic OR Left ventricular ejection fraction at rest greater than 40% and improves with exercise Pulmonary: Asymptomatic OR DLCO greater than 45% Other: Not pregnant or lactating HIV negative No uncontrolled viral, bacterial, or fungal infection

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior autologous or allogeneic bone marrow transplant Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: No concurrent mediastinal radiation No prior radiation therapy that would preclude total body irradiation Surgery: Not specified

• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Virginia Commonwealth University/Massey Cancer Center

Principal Investigators

Lee Ann Jensen, PhD

Role: STUDY_CHAIR

National Heart, Lung, and Blood Institute (NHLBI)

Locations

Stanford University Medical Center

Stanford, California, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Albert B. Chandler Medical Center, University of Kentucky

Lexington, Kentucky, United States

University of Minnesota Medical School

Minneapolis, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Western Pennsylvania Hospital

Pittsburgh, Pennsylvania, United States

University of South Carolina School of Medicine

Columbia, South Carolina, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Massey Cancer Center

Richmond, Virginia, United States

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Countries

United States

References

Lehtoranta L, Hibberd AA, Yeung N, Laitila A, Maukonen J, Ouwehand AC. Characterization of vaginal fungal communities in healthy women and women with bacterial vaginosis (BV); a pilot study. Microb Pathog. 2021 Dec;161(Pt A):105055. doi: 10.1016/j.micpath.2021.105055. Epub 2021 Jun 17.

Reference Type: DERIVED

PMID: 34146644 (View on PubMed)

Other Identifiers

P30CA016059

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCV-CCHR-9504-2X

Identifier Type: -

Identifier Source: secondary_id

DUMC-75951

Identifier Type: -

Identifier Source: secondary_id

NCI-G98-1388

Identifier Type: -

Identifier Source: secondary_id

CDR0000066016

Identifier Type: -

Identifier Source: org_study_id