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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT01177371

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

A Phase 2 study testing busulfan, cyclophosphamide and allogeneic bone marrow transplantation in people with Accelerated Phase Chronic Myelogenous Leukemia and Adult Acute Lymphoblastic Leukemia in Remission, run by Case Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Any age
What is being tested?
busulfan, cyclophosphamide and allogeneic bone marrow transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
Mar 1988to Feb 2010
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: High-dose Busulfan, High-dose Cyclophosphamide, and Allogeneic Bone Marrow Transplantation for Leukemia, Myelodysplastic Syndromes, Multiple Myeloma and Lymphoma

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.

Read the detailed description

OBJECTIVES:

  1. 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.

Being tested
busulfan, cyclophosphamide, allogeneic bone marrow transplantation, methylprednisolone, methotrexate
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Promyelocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • busulfanDrug

    Also called BSF, BU, Misulfan, Mitosan

    Given orally

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • allogeneic bone marrow transplantationProcedure or surgery

    Also called bone marrow therapy, allogeneic, bone marrow therapy, allogenic, transplantation, allogeneic bone marrow, transplantation, allogenic bone marrow

    Patients undergo allogeneic bone marrow transplant IV over 2-3 hours on day 0.

  • methylprednisoloneDrug

    Also called A-MethaPred, Depo-Medrol, Medrol, MePRDL

    Given IV or orally

  • methotrexateDrug

    Also called Abitrexate, amethopterin, Folex, methylaminopterin

    Given IV

  • cyclosporineDrug

    Also called 27-400, ciclosporin, cyclosporin, cyclosporin A

    Given IV or orally

Study groups in NCT01177371
Study groupRoleWhat they receive
Arm IExperimentalHIGH-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.
Receives: Drug: busulfan; Drug: cyclophosphamide; Procedure: allogeneic bone marrow transplantation; Drug: methylprednisolone; Drug: methotrexate; Drug: cyclosporine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: obtained at least one month apart beginning no earlier than two month after marrow infusion

  2. Toxicity as assessed by NCI CTC and engraftment (bone marrow) toxicity criteria

    Measured: twice weekly

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2010 (estimated)
  2. Study startMar 1988
  3. Primary completionFeb 2000
  4. Study completionFeb 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01177371
Sponsor's protocol ID
CWRU1494T
Other IDs
NCI-2010-01793
Status last verified
Aug 2010
First submitted
5 Aug 2010
Last updated
9 Aug 2010
Results posted
No
Data monitoring committee
Yes

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