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High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

Primary Purpose

Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Megakaryoblastic Leukemia (M7)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
busulfan
cyclophosphamide
allogeneic bone marrow transplantation
methylprednisolone
methotrexate
cyclosporine
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Accelerated Phase Chronic Myelogenous Leukemia

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Criteria

  • Acute non-lymphocytic leukemia (FAB types M1-M7) in first, or second remission, or early first or second bone or marrow relapse (>31% marrow blasts and no circulating peripheral blasts)
  • All patients with acute promyelocytic leukemia in first complete remission who have received retinoic acid and chemotherapy are not eligible
  • Acute lymphocytic leukemia in first or second remission, or early first or second bone marrow relapse (31% marrow blasts and no circulating peripheral blasts)
  • Pediatric ALL patients in first complete remission are not eligible
  • Chronic myelogenous leukemia in first or second chronic phase, or accelerated phase
  • Myelodysplastic syndrome =< 50 years
  • Lymphoma patients age =< 50 years (non Hodgkins or Hodgkins) in first or second relapse, or refractory disease, who are ineligible for autologous bone marrow transplantation because of tumor in the bone marrow
  • Multiple myeloma patients age =< 50 who have relapsed or are refractory to at least 2 chemo-radiation or chemotherapy regimens
  • Patients who have failed a previous allogeneic bone marrow transplant
  • Patients with inborn errors of metabolism
  • ECOG performance status of 0 or 1
  • Karnofsky performance status of >= 70%
  • Patients must be HTLV-III (HIV) anti-body negative
  • Acute and chronic leukemia patients must be age =< 50 years; patients up to age 60 years for any of these diseases who have a syngeneic donor are eligible
  • Patients (or bone marrow donors) who are HTLV-III (HIV) antibody positive are ineligible for this study
  • Patients must not have active infection
  • Patients must not have cytotoxic chemotherapeutic agents for at least 4 weeks before the transplant conditioning regimen is to begin
  • It is recommended but not required that acute leukemia patients undergoing transplantation in first remission must have received at least one course of consolidation therapy
  • Patients undergoing transplant in early relapse are eligible for transplant in first and second relapse only
  • Patients must have no history of acute myocardial infarction in the 6 months prior to transplantation, angina pectoris requiring nitrate therapy, uncontrolled major ventricular dysrhythmia, uncontrolled hypertension, or uncontrolled congestive heart failure
  • A gated-pool radionuclide scan fraction must be >= 50%
  • Serum creatinine must be =< 1.8% and a 24 hour creatinine clearance must be >= 60ml/min
  • Serum direct bilirubin >= 1.8mg%, or serum SGOT or SGPT > twice normal will exclude patients from this study
  • Severe symptomatic CNS disease of any etiology other than CNS leukemia will exclude patients from study
  • FEV1 and DLco (corrected) must be >= 60% of normal
  • pO2 > 60mmHg
  • Insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction render patients ineligible
  • Written informed consent must be obtained
  • Patients treated previously with radiation therapy in excess of 1000 cGy (rads) to any thoracic or abdominal port, or in excess of 3000 cGy (rads) to cranial-spinal ports, who are not eligible for other protocols are eligible for this study
  • DONOR: All genotypically HLA- or D/DR identical siblings are eligible to be bone marrow donors so long as their general medical condition permits the safe use of general or spinal anesthesia; selected donors who are not HLA-identical may be considered for use as long as they are D/DR identical, MLC compatible, and are in good condition to safely undergo spinal or general anesthesia
  • DONOR: This protocol will allow the use of donors who are unrelated but are HLA-A, b, C, D/Dr identical and MLC (mixed lymphocyte culture) compatible
  • Patient must have adequate insurance to cover the cost of the transplant and hospitalization

Sites / Locations

  • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6.

Outcomes

Primary Outcome Measures

Response rate
no evidence of leukemia as judged by two peripheral blood smears and two bone marrow aspirates and biopsies. Disease-free and overall survival data will be computed from the day of marrow infusion.
Toxicity as assessed by NCI CTC and engraftment (bone marrow) toxicity criteria

Secondary Outcome Measures

Full Information

First Posted
August 5, 2010
Last Updated
August 5, 2010
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01177371
Brief Title
High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma
Official Title
High-dose Busulfan, High-dose Cyclophosphamide, and Allogeneic Bone Marrow Transplantation for Leukemia, Myelodysplastic Syndromes, Multiple Myeloma and Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2010
Overall Recruitment Status
Completed
Study Start Date
March 1988 (undefined)
Primary Completion Date
February 2000 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Giving high doses of chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor bone marrow transplant helps stop the growth of cancer cells. It may also 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, methylprednisolone, and methotrexate after transplant may stop this from happening. PURPOSE: This clinical trial studies high-dose busulfan and high-dose cyclophosphamide followed by donor bone marrow transplant in treating patients with leukemia, myelodysplastic syndrome, multiple myeloma, or recurrent Hodgkin or Non-Hodgkin lymphoma.
Detailed Description
OBJECTIVES: I. To determine the toxicity and efficacy of the high-dose chemotherapy regimen which employs busulfan, cyclophosphamide, and allogeneic bone marrow transplantation. II. To ascertain feasibility (safety) and efficacy of the use of intensive chemotherapy regimen (busulfan and cyclophosphamide) followed by allogeneic bone marrow transplantation in patients with leukemia, myelodysplastic syndromes, multiple myeloma, and lymphoma. OUTLINE: HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2 . TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6 . After completion of study treatment, patients are followed up periodically.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Accelerated Phase Chronic Myelogenous Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Monoblastic Leukemia (M5a), Adult Acute Monocytic Leukemia (M5b), Adult Acute Myeloblastic Leukemia With Maturation (M2), Adult Acute Myeloblastic Leukemia Without Maturation (M1), Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), 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), Adult Acute Myelomonocytic Leukemia (M4), Adult Acute Promyelocytic Leukemia (M3), Adult Erythroleukemia (M6a), Adult Nasal Type Extranodal NK/T-cell Lymphoma, Adult Pure Erythroid Leukemia (M6b), Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Burkitt Lymphoma, Childhood Acute Erythroleukemia (M6), Childhood Acute Lymphoblastic Leukemia in Remission, Childhood Acute Megakaryocytic Leukemia (M7), Childhood Acute Monoblastic Leukemia (M5a), Childhood Acute Monocytic Leukemia (M5b), Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Myeloblastic Leukemia Without Maturation (M1), Childhood Acute Myeloid Leukemia in Remission, Childhood Acute Myelomonocytic Leukemia (M4), Childhood Acute Promyelocytic Leukemia (M3), Childhood Chronic Myelogenous Leukemia, Childhood Myelodysplastic Syndromes, Chronic Phase Chronic Myelogenous Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, De Novo Myelodysplastic Syndromes, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Peripheral T-Cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Previously Treated Myelodysplastic Syndromes, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Acute Myeloid Leukemia, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult Non-Hodgkin Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Refractory Multiple Myeloma, Relapsing Chronic Myelogenous Leukemia, Secondary Myelodysplastic Syndromes, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenstrom Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
HIGH-DOSE CHEMOTHERAPY: Patients receive oral busulfan every 6 hours on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 and -3, or -4 to -2. TRANSPLANTATION: Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0. GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine IV over 6 hours on day -1, over 10 hours twice daily on days 0-20, and then orally every 12 hours beginning on day 21 and continuing for 12 months with taper at 9 months. Patients also receive methylprednisolone IV or orally beginning on day 8 and continuing for 7 months with taper at 4 months. Some patients may also receive methotrexate IV on days 1, 3 and 6.
Intervention Type
Drug
Intervention Name(s)
busulfan
Other Intervention Name(s)
BSF, BU, Misulfan, Mitosan, Myeloleukon, Myelosan
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Other Intervention Name(s)
CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Other Intervention Name(s)
bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow
Intervention Description
Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Other Intervention Name(s)
A-MethaPred, Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort
Intervention Description
Given IV or orally
Intervention Type
Drug
Intervention Name(s)
methotrexate
Other Intervention Name(s)
Abitrexate, amethopterin, Folex, methylaminopterin, Mexate, MTX
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
27-400, ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given IV or orally
Primary Outcome Measure Information:
Title
Response rate
Description
no evidence of leukemia as judged by two peripheral blood smears and two bone marrow aspirates and biopsies. Disease-free and overall survival data will be computed from the day of marrow infusion.
Time Frame
obtained at least one month apart beginning no earlier than two month after marrow infusion
Title
Toxicity as assessed by NCI CTC and engraftment (bone marrow) toxicity criteria
Time Frame
twice weekly

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Criteria Acute non-lymphocytic leukemia (FAB types M1-M7) in first, or second remission, or early first or second bone or marrow relapse (>31% marrow blasts and no circulating peripheral blasts) All patients with acute promyelocytic leukemia in first complete remission who have received retinoic acid and chemotherapy are not eligible Acute lymphocytic leukemia in first or second remission, or early first or second bone marrow relapse (31% marrow blasts and no circulating peripheral blasts) Pediatric ALL patients in first complete remission are not eligible Chronic myelogenous leukemia in first or second chronic phase, or accelerated phase Myelodysplastic syndrome =< 50 years Lymphoma patients age =< 50 years (non Hodgkins or Hodgkins) in first or second relapse, or refractory disease, who are ineligible for autologous bone marrow transplantation because of tumor in the bone marrow Multiple myeloma patients age =< 50 who have relapsed or are refractory to at least 2 chemo-radiation or chemotherapy regimens Patients who have failed a previous allogeneic bone marrow transplant Patients with inborn errors of metabolism ECOG performance status of 0 or 1 Karnofsky performance status of >= 70% Patients must be HTLV-III (HIV) anti-body negative Acute and chronic leukemia patients must be age =< 50 years; patients up to age 60 years for any of these diseases who have a syngeneic donor are eligible Patients (or bone marrow donors) who are HTLV-III (HIV) antibody positive are ineligible for this study Patients must not have active infection Patients must not have cytotoxic chemotherapeutic agents for at least 4 weeks before the transplant conditioning regimen is to begin It is recommended but not required that acute leukemia patients undergoing transplantation in first remission must have received at least one course of consolidation therapy Patients undergoing transplant in early relapse are eligible for transplant in first and second relapse only Patients must have no history of acute myocardial infarction in the 6 months prior to transplantation, angina pectoris requiring nitrate therapy, uncontrolled major ventricular dysrhythmia, uncontrolled hypertension, or uncontrolled congestive heart failure A gated-pool radionuclide scan fraction must be >= 50% Serum creatinine must be =< 1.8% and a 24 hour creatinine clearance must be >= 60ml/min Serum direct bilirubin >= 1.8mg%, or serum SGOT or SGPT > twice normal will exclude patients from this study Severe symptomatic CNS disease of any etiology other than CNS leukemia will exclude patients from study FEV1 and DLco (corrected) must be >= 60% of normal pO2 > 60mmHg Insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal dysfunction render patients ineligible Written informed consent must be obtained Patients treated previously with radiation therapy in excess of 1000 cGy (rads) to any thoracic or abdominal port, or in excess of 3000 cGy (rads) to cranial-spinal ports, who are not eligible for other protocols are eligible for this study DONOR: All genotypically HLA- or D/DR identical siblings are eligible to be bone marrow donors so long as their general medical condition permits the safe use of general or spinal anesthesia; selected donors who are not HLA-identical may be considered for use as long as they are D/DR identical, MLC compatible, and are in good condition to safely undergo spinal or general anesthesia DONOR: This protocol will allow the use of donors who are unrelated but are HLA-A, b, C, D/Dr identical and MLC (mixed lymphocyte culture) compatible Patient must have adequate insurance to cover the cost of the transplant and hospitalization
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hillard Lazarus
Organizational Affiliation
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States

12. IPD Sharing Statement

Learn more about this trial

High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

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