search
Back to results

Bone Marrow Transplant in Treating Patients With Hematologic Cancers

Primary Purpose

Chronic Myeloproliferative Disorders, Leukemia, Multiple Myeloma and Malignant Plasma Cell Neoplasms

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
busulfan
Cyclophosphamide
VP-16
Fractionated Total Body Irradiation (FTBI)
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring refractory multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, refractory chronic lymphocytic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, polycythemia vera, primary myelofibrosis, essential thrombocythemia, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, previously treated myelodysplastic syndromes, refractory cytopenia with multilineage dysplasia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, 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

Eligibility Criteria

15 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of: Acute myelogenous leukemia Complete remission (CR) 1 - ALL except good cytogenetics defined as [(inv16, t(8,21), t(15,17)] CR2 Induction failures Relapsed OR Acute lymphocytic leukemia (ALL) CR1 - high risk defined as overt CNS involvement, 1 or more risk factors (age 30 and over, WBC at least 20,000/mm^3, at least 4 weeks to CR1, myeloid phenotype) CR2 Induction failures Relapsed OR Chronic myelogenous leukemia Chronic phase (CP) 1 Accelerated phase (AP)/CP2 OR Chronic lymphocytic leukemia At diagnosis - RAI stage III/IV or Binet C Must undergo 1 induction regimen Relapsed - any stage Must have received no more than 3 regimens for diagnosis OR Multiple myeloma At diagnosis - stage II/III (primary refractory or sensitive) Relapsed no more than 2 times - sensitive disease Plasma cell leukemia OR Myelodysplasia All subtypes eligible OR Myeloproliferative disorders Poor response to medical therapy OR Cytogenetic abnormalities Must have a related donor who is genotypic 6 out of 6 HLA A, B, and DR match Molecular DR matching required PATIENT CHARACTERISTICS: Age: 15 to 55 Performance status: Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 3 times upper limit of normal PT/PTT normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: LVEF at least 45% by MUGA scan or echocardiography No myocardial infarction within the past 6 months No arrhythmias controlled by therapy Pulmonary: FEV_1 at least 50% predicted DLCO at least 50% predicted Other: Not pregnant or nursing Negative pregnancy test No diabetes mellitus or thyroid disease that is not medically controlled No psychosocial disorder that would preclude study compliance No active serious infections HIV negative Donor must be HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

BuCy2

VP16/TBI

Arm Description

Busulfan & Cyclophosphamide

Fractionated Total Body Irradiation + VP-16

Outcomes

Primary Outcome Measures

Relapse-free survival
Relapse free survival 5 post transplant deteremiend by the Kaplan-Meier product-limit method.

Secondary Outcome Measures

Full Information

First Posted
June 2, 2000
Last Updated
December 9, 2020
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00005797
Brief Title
Bone Marrow Transplant in Treating Patients With Hematologic Cancers
Official Title
Allogeneic Bone Marrow Transplantation for Hematologic Malignancies: A Treatment Approach Based on Risk of Relapse and Toxicity
Study Type
Interventional

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
March 1993 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Giving chemotherapy drugs and total-body irradiation before a donor bone marrow 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. PURPOSE: This phase II trial is studying how well donor bone marrow transplant works in treating patients with hematologic cancers.
Detailed Description
OBJECTIVES: Determine the progression free survival (PFS) and overall survival (OS) of patients with low risk myeloid disorders or older allogeneic recipients who are treated with high dose busulfan and cyclophosphamide and allogeneic bone marrow transplantation (BMT). Determine the PFS and OS in patients with lymphoid and high risk myeloid disorders who are treated with etoposide, total body irradiation, and allogeneic BMT. Evaluate the toxicities of these 2 regimens when combined with cyclosporine and methotrexate as graft versus host disease prophylaxis in these patients. Evaluate the PFS and OS of allogeneic BMT in patients with multiple myeloma and chronic lymphocytic leukemia. OUTLINE: Regimen A: Patients with chronic myelogenous leukemia (CP1, AP/CP2) and other myeloproliferative disorders, myelodysplastic disorders, acute myelogenous leukemia (CR1), or multiple myeloma (not eligible to receive total body irradiation due to prior radiation) are treated with high dose busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation (BMT). Patients receive oral busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. Allogeneic bone marrow is infused on day 0. Regimen B: Patients with acute myelogenous leukemia (at least CR2, relapsed), acute lymphoid leukemia (ALL), any acute leukemia with CNS involvement, multiple myeloma, or chronic lymphocytic leukemia are treated with total body irradiation and etoposide followed by allogeneic BMT. Patients receive total body irradiation (TBI) on days -7 to -4 for a total of 11 fractions and etoposide IV over 4 hours on day -3. Male patients with ALL receive a testicular boost in 2 fractions on 2 successive days during TBI. Allogeneic bone marrow is infused on day 0. Patients in both regimens receive cyclosporine and methotrexate as graft versus host disease prophylaxis. Patients are followed weekly for 3 months and then monthly for 1 year. PROJECTED ACCRUAL: At least 50 patients with low risk myeloid disease, 50 patients with lymphoid malignancies, and 60 patients with high risk myeloid disease will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Leukemia, Multiple Myeloma and Malignant Plasma Cell Neoplasms, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
refractory multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, refractory chronic lymphocytic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, polycythemia vera, primary myelofibrosis, essential thrombocythemia, refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, previously treated myelodysplastic syndromes, refractory cytopenia with multilineage dysplasia, chronic eosinophilic leukemia, chronic neutrophilic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
125 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BuCy2
Arm Type
Other
Arm Description
Busulfan & Cyclophosphamide
Arm Title
VP16/TBI
Arm Type
Other
Arm Description
Fractionated Total Body Irradiation + VP-16
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
Busulfex®
Intervention Description
administered on Day -7 through Day -4. The total dose is 12.8 mg/kg
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
administered at a dose of 60 mg/kg on each of two successive days (Days -3 and -2)
Intervention Type
Drug
Intervention Name(s)
VP-16
Other Intervention Name(s)
Etoposide (VP-16; Vepesid(R) brand only)
Intervention Description
administered as a single infusion on Day -3. The dose is 60 mg/kg and is calculated on actual body weight unless the patient's weight is >/= 150% of IBW, in which case adjusted body weight will be used.
Intervention Type
Radiation
Intervention Name(s)
Fractionated Total Body Irradiation (FTBI)
Intervention Description
FTBI is performed on day -7 through day -4. The total dose of radiation is 1,320 cGy.
Primary Outcome Measure Information:
Title
Relapse-free survival
Description
Relapse free survival 5 post transplant deteremiend by the Kaplan-Meier product-limit method.
Time Frame
5 years post transplant

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of: Acute myelogenous leukemia Complete remission (CR) 1 - ALL except good cytogenetics defined as [(inv16, t(8,21), t(15,17)] CR2 Induction failures Relapsed OR Acute lymphocytic leukemia (ALL) CR1 - high risk defined as overt CNS involvement, 1 or more risk factors (age 30 and over, WBC at least 20,000/mm^3, at least 4 weeks to CR1, myeloid phenotype) CR2 Induction failures Relapsed OR Chronic myelogenous leukemia Chronic phase (CP) 1 Accelerated phase (AP)/CP2 OR Chronic lymphocytic leukemia At diagnosis - RAI stage III/IV or Binet C Must undergo 1 induction regimen Relapsed - any stage Must have received no more than 3 regimens for diagnosis OR Multiple myeloma At diagnosis - stage II/III (primary refractory or sensitive) Relapsed no more than 2 times - sensitive disease Plasma cell leukemia OR Myelodysplasia All subtypes eligible OR Myeloproliferative disorders Poor response to medical therapy OR Cytogenetic abnormalities Must have a related donor who is genotypic 6 out of 6 HLA A, B, and DR match Molecular DR matching required PATIENT CHARACTERISTICS: Age: 15 to 55 Performance status: Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT/SGPT no greater than 3 times upper limit of normal PT/PTT normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 60 mL/min Cardiovascular: LVEF at least 45% by MUGA scan or echocardiography No myocardial infarction within the past 6 months No arrhythmias controlled by therapy Pulmonary: FEV_1 at least 50% predicted DLCO at least 50% predicted Other: Not pregnant or nursing Negative pregnancy test No diabetes mellitus or thyroid disease that is not medically controlled No psychosocial disorder that would preclude study compliance No active serious infections HIV negative Donor must be HIV negative PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Teresa Field, MD, PhD
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Study Chair
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Bone Marrow Transplant in Treating Patients With Hematologic Cancers

We'll reach out to this number within 24 hrs