Chronic Myeloproliferative DisordersPhase 2NCT00281879

Donor Stem Cell Transplant or Donor White Blood Cell Infusions in Treating Patients With Hematologic Cancer

A Phase 2 study testing anti-thymocyte globulin, filgrastim and busulfan in people with Chronic Myeloproliferative Disorders and Leukemia, run by OHSU Knight Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages Up to 60 years
Conditions the study is for: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
What is being tested?: anti-thymocyte globulin, filgrastim and busulfan
Type of treatment: Pill or oral medicine, Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 1 siteUnited States
Study dates: Feb 2006to Mar 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 Up to 60 years
All sexes
No healthy volunteers
Child, Adult

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following*:
Acute lymphoblastic leukemia in any disease phase
Patients with any of the following high-risk features are encouraged to enroll:
Philadelphia chromosome positive disease
L3 morphology, especially in the presence of t(8;14), t(8;22), or t(2;8)
Patients not in remission at day 28 of first induction
High LDH (i.e., ≥ 300 IU/mL at presentation)
Pre-B-cell, mixed lineage, or Burkitt's markers
Relapsed in the marrow while receiving continuous chemotherapy
Within 6 months after stopping chemotherapy
Relapse in one organ or extramedullary relapses in more than one organ while still receiving chemotherapy
Hodgkin's or non-Hodgkin's lymphoma beyond first complete remission (CR) or in first CR with features of high-risk disease, including, but not limited to:
Lymphoma not in CR after 3 courses of primary therapy
Patients with bulky disease at presentation, especially bulky mediastinal disease
Patients with LDH ≥ 300 IU/mL at presentation
Patients with extranodal disease
Patients with first remission within less than 1 year
Stage IV disease at presentation, especially with marrow involvement
Patients with high-intermediate or high International Index Scores
Acute myeloid leukemia (AML) meeting the following criteria:
Beyond first remission or high-risk disease in first CR
Required multiple courses of induction therapy to achieve a remission
Had residual leukemia on day 14-28 bone marrow examination after initial induction
Patients with any cytogenetic abnormality except inv 16 or t(8;21)
Chronic myelogenous leukemia in the chronic or early accelerated phase of the disease
Patients with blast crisis that can be induced back into chronic phase may be transplanted in second chronic phase
Myelodysplastic syndromes (MDS) meeting the following requirements:
Transfusion-dependent refractory anemia (RA), RA with excess blasts (RAEB), RAEB in transformation, or chronic myelomonocytic leukemia (CMML)
Patients with MDS that present with or evolve to AML must be re-induced back to remission prior to initiating a search for an unrelated donor NOTE: *Patients with other hematologic malignancies not listed above, including diseases such as chronic lymphocytic leukemia (CLL), multiple myeloma, or rare pediatric malignancies, or patients who are felt to be at high-risk for relapse but who do not have features listed, may be allowed at the discretion of the investigator.
Must have failed prior stem cell transplantation
Must have a suitable unrelated allogeneic hematopoietic stem cell donor
A 5/6 match degree is acceptable for unrelated bone marrow donors
A 4/6 match degree is acceptable for unrelated cord blood units

PATIENT CHARACTERISTICS:

SWOG performance status (PS) 0-2 OR
Karnofsky PS 50-100% OR
Lansky PS 50-100%
Creatinine clearance ≥ 45 mL/min
Creatinine ≤ 2.5 mg/dL
Bilirubin ≤ 2 mg/dL (abnormally high liver function tests allowed if the only source for the elevation is due to lymphoma of the liver)
AST or ALT ≤ 2 times normal (abnormally high liver function tests allowed if the only source for the elevation is due to lymphoma of the liver)
No patients at high risk of veno-occlusive disease
Not pregnant or nursing
Negative serum pregnancy test
Fertile patients must use an effective contraceptive method
DLCO ≥ 50% of predicted
FEV_1/FVC ≥ 65% of predicted
No current congestive heart failure (CHF) and/or LVEF ≥ 45%
No myocardial infarction within the past 6 months
No unstable angina within the past 6 months
HIV negative
Life expectancy must not be limited by disease other than malignancy
No allergy to any chemotherapeutic agent included in the regimen

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Trial locations and contacts

1 site in 1 country.

United States1 site

OHSU Knight Cancer Institute
Portland, Oregon, 97239-3098

Other trials in United States

About this study

Official title: Transplantation of Unrelated Donor Hematopoietic Stem Cells for the Treatment of Hematological Malignancies

RATIONALE: A peripheral stem cell transplant or an umbilical cord blood transplant from a donor may be able to replace blood-forming cells that were destroyed by chemotherapy or radiation therapy. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) after the transplant may help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells can make an immune response against the body's normal cells. Methotrexate, cyclosporine, tacrolimus, or methylprednisolone may stop this from happening.

PURPOSE: This clinical trial is studying how well a donor stem cell transplant or donor white blood cell infusions work in treating patients with hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of patients with high-risk hematologic malignancies.
Compare survival, disease-free survival (DFS), response rate, and toxicity rates in these patients with historical controls.
Compare the rate and severity of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation in patients with hematopoietic malignancies with historical controls transplanted with stem cells from related sibling donors
Assess engraftment, long-term hematopoietic recovery, relapse rate, and disease-free survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients with high-risk hematological malignancies.
Assess engraftment, long-term hematopoietic recovery, and overall survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients who have graft failure or graft rejection.
Compare engraftment, long-term hematopoietic recovery, rate of GVHD, rate of relapse, toxicity rates, overall disease-free survival and overall survival when donor leukocyte infusions (DLI) are given for patients who have disease recurrence, progression, or low donor chimerisms after unrelated stem cell transplantation or before DLI with historical controls of other donor leukocyte infusions.

Secondary

Determine the quality of life of patients undergoing hematopoietic stem cell transplantation or donor leukocyte infusions from unrelated HLA genotypically-identical donors.

OUTLINE: Patients are assigned to 1 of 8 treatment groups.

Group 1*: Patients undergo total body irradiation (TBI) twice a day on days -7 to -4. Patients then receive cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo stem cell transplantation (SCT). Beginning on day 7, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
Group 2 (patients who have previously experienced dose-limiting radiotherapy): Patients receive oral busulfan 4 times daily on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
Group 3 (pediatric patients only): Patients receive busulfan IV 4 times daily on days -9 to -6 and cyclophosphamide IV over 1 hour and fludarabine IV over 30 minutes on days -5 to -2. On day 0 patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
Group 4 (second SCT for patients who have experienced graft rejection or failure)*: Patients receive low-dose fludarabine IV over 30 minutes on days -4 to -2. Patients then undergo low-dose TBI once followed by SCT on day 0. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
Group 5 (patients who developed grade 3 cystitis after prior cyclophosphamide-containing therapy): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours and cytarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -1 (BEAM). On day 0, patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
Group 6 (cord blood transplantation): Patients receive anti-thymocyte globulin IV once daily and methylprednisolone IV twice daily on days -3 to -1. On day 0, patients undergo an umbilical cord blood SCT.
Group 7 (patients with relapsing or progressive disease after prior transplants or low donor chimerisms)*: Patients must not have existing graft-versus-host disease (GVHD). Patients receive donor lymphocyte infusions with conditioning chemotherapy and/or radiotherapy at the discretion of the investigator.
Group 8 (pediatric patients only)*: Patients undergo TBI twice a day on days -7 to -5. Patients also receive etoposide IV over 24 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0, patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.

NOTE: *Patients who have received > 3000 cGy to the central nervous system or > 2000 cGy to the lung or liver may not receive any regimen containing total body irradiation (TBI)

All patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11; cyclosporine and/or tacrolimus on days -2 to 100; and/or methylprednisolone IV on days 7 to 100.

Patients with an unrelated donor who experience a relapse prior to transplantation, may proceed directly to transplantation. However, if immediate transplantation from the unrelated donor is not possible, the patient must be re-induced into a complete hematological remission. Patients who experience graft failure or graft rejection after allogeneic transplantation are eligible for a second stem cell infusion from the original donor.

Quality of life is assessed at baseline and at 7 days, 3 months, and 1 year after transplantation.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Being tested: anti-thymocyte globulin, filgrastim, busulfan, carmustine, cyclophosphamide
Keywords: adult acute lymphoblastic leukemia in remission, L1 adult acute lymphoblastic leukemia, L2 adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, L1 childhood acute lymphoblastic leukemia, L2 childhood acute lymphoblastic leukemia, L3 childhood acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities
Medical subject headings: Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

anti-thymocyte globulinBiological
Also called ATG
Intravenous, 1.5 mg/kg of body weight daily for 7 to 14 days The first dose should be administered over a minimum of 6 hours and over at least 4 hours on subsequent doses through a high-flow vein.
filgrastimBiological
Also called G-CSF
Will be given IV at 5 µg/kg/day. The first injection will be administered on day +7, i.e. 7 days after the hematopoietic stem cells are infused.
Will be administered until the ANC is 1500 / µl for 2 days. Dose and schedule of G-CSF administration is left to each center's discretion.
busulfanDrug
Patients who take the drug PO, busulfan will be administered at 1 mg/kg/ dose given by mouth every 6 hours for 16 consecutive doses. Pediatric patients who receive busulfan IV continuous infusion will receive a dose of 3.0 mg/kg/IBW if under the age of 2.Pediatric patients over the age of 2 will receive busulfan at a dose of 0.8 mg/kg/dose.
carmustineDrug
300mg/m2 IV dissolved in 500 cc NS infused over 2 hours into right atrial catheter on day -6.
cyclophosphamideDrug
For transplantation, the drug is diluted in 250 to 500 cc of NS or D5W and administered IV over 2 hours.
cyclosporineDrug
Initial doses will be administered IV at a starting dose of 1.5 mg/kg BID. The infusion will vary from 2-24hr depending on the incidence of side-effects.
cytarabineDrug
400 mg/m2 dissolved in 200cc D5W and infused over 30 minutes into right atrial catheter on days -5, -4, -3, -2.
etoposideDrug
Etoposide administration 200 mg /m2 dissolved in 1 liter NS and infused over 2 hours into right atrial catheter. Infusion to begin after cytarabine administration on days -5, -4, -3, -2.
Etoposide administration 50 mg/kg IV over 24 hours, divided into 3 doses. Dilute in normal saline at a concentration of 0.4 mg/ml (Observe for precipitation). Administered IV with continuous infusion over 24 hours. Diuretics may be given for fluid overload.
fludarabine phosphateDrug
Fludarabine administered at 30 mg/m2 IVPB infused over 30 minutes into right atrial catheter on days -4, -3, -2.
Fludarabine administered at 40 mg/m2 IVPB infused over 30 into the right atrial catheter on days -5, -4, -3, and -2.
melphalanDrug
140 mg /m2 in concentration of 0.45 mg/ml of NS infused over 30 minutes into right atrial catheter on day -1.
methotrexateDrug
Administered on days +1, +3, and +7.
methylprednisoloneDrug
Methyl-prednisolone is administered IV as a rapid infusion.
mycophenolate mofetilDrug
Mycophenolate may be used as a substitute for Methotrexate
tacrolimusDrug
Also called FK-506
A drug used to decrease the risk of graft versus host disease (GvHD).
peripheral blood stem cell transplantationProcedure or surgery
The stem cells will be given to you by intravenous injection (through your vein) using a catheter that was placed prior to beginning chemotherapy. The stem cell infusion takes 1-6 hours.
umbilical cord blood transplantationProcedure or surgery
The patient will receive ATG to improve the changes of engraftment and decrease their risk of graft versus host disease. The patient may receive ATG 3 times during their transplant regimen on days -3 through days -1
radiation therapyRadiation
Radiation will be given to you 2 times a day for 3 or 4 days.

Study groups in NCT00281879
Study group	Role	What they receive
Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI)	Active comparator	Not described Receives: Biological: filgrastim; Drug: cyclophosphamide; Drug: cyclosporine; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy
Busulfan and Cyclophosphamide (Cytoxan)	Active comparator	Not described Receives: Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: cyclosporine; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation
BEAM Regimen	Active comparator	On the day of your admission, you will start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. Chemotherapy will begin on Day -6 with carmustine (BCNU), followed by etoposide (VP-16), cytosine arabinoside (ARA-C), and melphalan. This conditioning regimen is known as the BEAM regimen. The dose of this therapy is high enough to kill cancer cells but will also kill all of your normal blood forming cells. Subjects undergoing the BEAM regimen will not have total body irradiation (TBI). Receives: Biological: filgrastim; Drug: carmustine; Drug: cyclosporine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation
Low-Dose Fludarabine and TBI(for second stem cell donation)	Active comparator	A conditioning regimen of low-dose fludarabine and TBI is used in the event that a second donation of hematopoietic stem cells is necessary. Chemotherapy with Fludarabine will begin 4 days prior to your transplant. This drug will be given through the catheter in your chest daily for 3 days. TBI (radiation) will be given to you on the day of your transplant. After your TBI, your donor's stem cells / bone marrow will be given to you through your catheter. The drugs cyclosporine and mycophenolate mofetil (MMF) will be given orally to help you accept your donor's cells. Receives: Biological: filgrastim; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy
Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only)	Active comparator	On the day of your admission you will start to take a drug called Dilantin which is used to help prevent seizures while you receive your chemotherapy drugs. You will also start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. On the next day, you will then begin your conditioning therapy with a drug called busulfan. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm four times per day for four days. After the busulfan treatment, you will receive 4 doses each of two drugs, cyclophosphamide (also known as Cytoxan) and fludarabine, over 2 hours into your vein. Receives: Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation
ATG For Cord Blood Transplants	Active comparator	If you are undergoing a pre-transplant conditioning regimen prior to undergoing a cord blood transplant, you will receive a drug called ATG to improve your chances of engraftment and decrease your risk of graft versus host disease. You may receive ATG 3 times during your transplant regimen on days -3 through days -1 in addition to your pre-transplant conditioning therapy. Methylprednisolone will also be given during each dose of ATG to help reduce any reactions during infusion. Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: cyclosporine; Drug: methotrexate; Drug: methylprednisolone; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation; Procedure: umbilical cord blood transplantation
DLI (Donor Leukocyte Infusion)	Active comparator	Donor Leukocyte Infusions: You will receive DLI from your original transplant donor. This will be given through a vein , usually in your arm. It will be similar to getting a platelet or blood transfusion. You may require more than one DLI. The decision to give you another infusion will be determined by your condition, relapse status, GVHD and how much DLI you were given before. You may need chemotherapy and/or radiation to improve your disease status prior to additional DLI's. Receives: Biological: filgrastim; Drug: cyclosporine; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation
Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only)	Active comparator	On the day after your admission, you will start receiving radiation therapy (TBI). Radiation will be given to you 2 times a day for 3 days. On the next day, you will then begin your chemotherapy with a drug called etoposide. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm for one day. After the etoposide treatment, on the next day you will receive cyclophosphamide (also known as Cytoxan) for 2 days. When you are given cyclophosphamide, you will also be given a medication called MESNA to help protect your bladder from damage. After you have completed the cyclophosphamide you will rest one day without any anti-cancer therapy. This allows your body time to remove and inactivate the chemotherapy. After a day of rest, you will be given your donor's cells. Receives: Biological: filgrastim; Drug: cyclophosphamide; Drug: cyclosporine; Drug: etoposide; Drug: methotrexate; Drug: mycophenolate mofetil; Drug: tacrolimus; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

What is being measured

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

Number of Participants With Disease Free Survival (DFS).
Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of high-risk hematopoietic malignancies.
Disease-free survival: The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer.
Measured: Duration of the study; Up to 2 years

Timeline

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

Feb 2006Mar 2008

First posted25 Jan 2006 (estimated)
Study startFeb 2006
Primary completionFeb 2008
Study completionMar 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
More trials run by OHSU Knight Cancer InstituteThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 200 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00281879
Sponsor's protocol ID: CDR0000452794
Other IDs: P30CA016058, OHSU-TPI-9695-L, OHSU-540
Status last verified: Sep 2017
First submitted: 24 Jan 2006
Last updated: 27 Sep 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia

All Chronic Myeloproliferative Disorders trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Transplantation of Unrelated Donor Hematopoietic Stem Cells for the Treatment of Hematological Malignancies
ClinicalTrials.gov ID: NCT00281879
Acronym / sponsor ID: CDR0000452794
Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords: adult acute lymphoblastic leukemia in remission, L1 adult acute lymphoblastic leukemia, L2 adult acute lymphoblastic leukemia, L3 adult acute lymphoblastic leukemia, recurrent adult acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 200 participants (actual)
Lead sponsor: OHSU Knight Cancer InstituteUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Feb 2006
Primary completion: Feb 2008 (actual)
Study completion: Mar 2008 (actual)
First posted: 25 Jan 2006 (estimated)
Results: Posted 19 Jun 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

PURPOSE: This clinical trial is studying how well a donor stem cell transplant or donor white blood cell infusions work in treating patients with hematologic cancer.

Detailed description

OBJECTIVES:

Primary

Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of patients with high-risk hematologic malignancies.
Compare survival, disease-free survival (DFS), response rate, and toxicity rates in these patients with historical controls.
Compare the rate and severity of acute and chronic GVHD after allogeneic hematopoietic stem cell transplantation in patients with hematopoietic malignancies with historical controls transplanted with stem cells from related sibling donors
Assess engraftment, long-term hematopoietic recovery, relapse rate, and disease-free survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients with high-risk hematological malignancies.
Assess engraftment, long-term hematopoietic recovery, and overall survival when allogeneic hematopoietic stem cells are used as a source of stem cells for transplantation in patients who have graft failure or graft rejection.
Compare engraftment, long-term hematopoietic recovery, rate of GVHD, rate of relapse, toxicity rates, overall disease-free survival and overall survival when donor leukocyte infusions (DLI) are given for patients who have disease recurrence, progression, or low donor chimerisms after unrelated stem cell transplantation or before DLI with historical controls of other donor leukocyte infusions.

Secondary

Determine the quality of life of patients undergoing hematopoietic stem cell transplantation or donor leukocyte infusions from unrelated HLA genotypically-identical donors.

OUTLINE: Patients are assigned to 1 of 8 treatment groups.

Group 1*: Patients undergo total body irradiation (TBI) twice a day on days -7 to -4. Patients then receive cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo stem cell transplantation (SCT). Beginning on day 7, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
Group 2 (patients who have previously experienced dose-limiting radiotherapy): Patients receive oral busulfan 4 times daily on days -7 to -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0 patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
Group 3 (pediatric patients only): Patients receive busulfan IV 4 times daily on days -9 to -6 and cyclophosphamide IV over 1 hour and fludarabine IV over 30 minutes on days -5 to -2. On day 0 patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
Group 4 (second SCT for patients who have experienced graft rejection or failure)*: Patients receive low-dose fludarabine IV over 30 minutes on days -4 to -2. Patients then undergo low-dose TBI once followed by SCT on day 0. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.
Group 5 (patients who developed grade 3 cystitis after prior cyclophosphamide-containing therapy): Patients receive carmustine IV over 2 hours on day -6, etoposide IV over 2 hours and cytarabine IV over 30 minutes on days -5 to -2, and melphalan IV over 30 minutes on day -1 (BEAM). On day 0, patients undergo SCT. Beginning on day 7, patients receive G-CSF IV once daily until blood counts recover.
Group 6 (cord blood transplantation): Patients receive anti-thymocyte globulin IV once daily and methylprednisolone IV twice daily on days -3 to -1. On day 0, patients undergo an umbilical cord blood SCT.
Group 7 (patients with relapsing or progressive disease after prior transplants or low donor chimerisms)*: Patients must not have existing graft-versus-host disease (GVHD). Patients receive donor lymphocyte infusions with conditioning chemotherapy and/or radiotherapy at the discretion of the investigator.
Group 8 (pediatric patients only)*: Patients undergo TBI twice a day on days -7 to -5. Patients also receive etoposide IV over 24 hours on day -4 and cyclophosphamide IV over 1 hour on days -3 and -2. On day 0, patients undergo SCT. Beginning on day 7, patients may receive G-CSF IV once daily until blood counts recover.

NOTE: *Patients who have received > 3000 cGy to the central nervous system or > 2000 cGy to the lung or liver may not receive any regimen containing total body irradiation (TBI)

All patients receive GVHD prophylaxis comprising methotrexate IV on days 1, 3, 6, and 11; cyclosporine and/or tacrolimus on days -2 to 100; and/or methylprednisolone IV on days 7 to 100.

Quality of life is assessed at baseline and at 7 days, 3 months, and 1 year after transplantation.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI)	Active comparator	Biological: filgrastim, Drug: cyclophosphamide, Drug: cyclosporine, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantation, Radiation: radiation therapy
Busulfan and Cyclophosphamide (Cytoxan)	Active comparator	Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: cyclosporine, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantation
BEAM Regimen	Active comparator	Biological: filgrastim, Drug: carmustine, Drug: cyclosporine, Drug: cytarabine, Drug: etoposide, Drug: melphalan, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantationOn the day of your admission, you will start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. Chemotherapy will begin on Day -6 with carmustine (BCNU), followed by etoposide (VP-16), cytosine arabinoside (ARA-C), and melphalan. This conditioning regimen is known as the BEAM regimen. The dose of this therapy is high enough to kill cancer cells but will also kill all of your normal blood forming cells. Subjects undergoing the BEAM regimen will not have total body irradiation (TBI).
Low-Dose Fludarabine and TBI(for second stem cell donation)	Active comparator	Biological: filgrastim, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantation, Radiation: radiation therapyA conditioning regimen of low-dose fludarabine and TBI is used in the event that a second donation of hematopoietic stem cells is necessary. Chemotherapy with Fludarabine will begin 4 days prior to your transplant. This drug will be given through the catheter in your chest daily for 3 days. TBI (radiation) will be given to you on the day of your transplant. After your TBI, your donor's stem cells / bone marrow will be given to you through your catheter. The drugs cyclosporine and mycophenolate mofetil (MMF) will be given orally to help you accept your donor's cells.
Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only)	Active comparator	Biological: filgrastim, Drug: busulfan, Drug: cyclophosphamide, Drug: cyclosporine, Drug: fludarabine phosphate, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantationOn the day of your admission you will start to take a drug called Dilantin which is used to help prevent seizures while you receive your chemotherapy drugs. You will also start to take a drug called allopurinol which helps to protect your kidneys as your body works to discharge cells killed off by your chemotherapy and TBI. On the next day, you will then begin your conditioning therapy with a drug called busulfan. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm four times per day for four days. After the busulfan treatment, you will receive 4 doses each of two drugs, cyclophosphamide (also known as Cytoxan) and fludarabine, over 2 hours into your vein.
ATG For Cord Blood Transplants	Active comparator	Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: cyclosporine, Drug: methotrexate, Drug: methylprednisolone, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantation, Procedure: umbilical cord blood transplantationIf you are undergoing a pre-transplant conditioning regimen prior to undergoing a cord blood transplant, you will receive a drug called ATG to improve your chances of engraftment and decrease your risk of graft versus host disease. You may receive ATG 3 times during your transplant regimen on days -3 through days -1 in addition to your pre-transplant conditioning therapy. Methylprednisolone will also be given during each dose of ATG to help reduce any reactions during infusion.
DLI (Donor Leukocyte Infusion)	Active comparator	Biological: filgrastim, Drug: cyclosporine, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantationDonor Leukocyte Infusions: You will receive DLI from your original transplant donor. This will be given through a vein , usually in your arm. It will be similar to getting a platelet or blood transfusion. You may require more than one DLI. The decision to give you another infusion will be determined by your condition, relapse status, GVHD and how much DLI you were given before. You may need chemotherapy and/or radiation to improve your disease status prior to additional DLI's.
Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only)	Active comparator	Biological: filgrastim, Drug: cyclophosphamide, Drug: cyclosporine, Drug: etoposide, Drug: methotrexate, Drug: mycophenolate mofetil, Drug: tacrolimus, Procedure: peripheral blood stem cell transplantation, Radiation: radiation therapyOn the day after your admission, you will start receiving radiation therapy (TBI). Radiation will be given to you 2 times a day for 3 days. On the next day, you will then begin your chemotherapy with a drug called etoposide. This medicine will be given to you by an infusion into your bloodstream through a small tube in the vein of your arm for one day. After the etoposide treatment, on the next day you will receive cyclophosphamide (also known as Cytoxan) for 2 days. When you are given cyclophosphamide, you will also be given a medication called MESNA to help protect your bladder from damage. After you have completed the cyclophosphamide you will rest one day without any anti-cancer therapy. This allows your body time to remove and inactivate the chemotherapy. After a day of rest, you will be given your donor's cells.

Who may qualify

Ages: Up to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
anti-thymocyte globulinAlso: ATGIntravenous, 1.5 mg/kg of body weight daily for 7 to 14 days The first dose should be administered over a minimum of 6 hours and over at least 4 hours on subsequent doses through a high-flow vein.	Biological	ATG For Cord Blood Transplants
filgrastimAlso: G-CSFWill be given IV at 5 µg/kg/day. The first injection will be administered on day +7, i.e. 7 days after the hematopoietic stem cells are infused. Will be administered until the ANC is 1500 / µl for 2 days. Dose and schedule of G-CSF administration is left to each center's discretion.	Biological	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
busulfanPatients who take the drug PO, busulfan will be administered at 1 mg/kg/ dose given by mouth every 6 hours for 16 consecutive doses. Pediatric patients who receive busulfan IV continuous infusion will receive a dose of 3.0 mg/kg/IBW if under the age of 2.Pediatric patients over the age of 2 will receive busulfan at a dose of 0.8 mg/kg/dose.	Drug	Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only)
carmustine300mg/m2 IV dissolved in 500 cc NS infused over 2 hours into right atrial catheter on day -6.	Drug	BEAM Regimen
cyclophosphamideFor transplantation, the drug is diluted in 250 to 500 cc of NS or D5W and administered IV over 2 hours.	Drug	Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only)
cyclosporineInitial doses will be administered IV at a starting dose of 1.5 mg/kg BID. The infusion will vary from 2-24hr depending on the incidence of side-effects.	Drug	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
cytarabine400 mg/m2 dissolved in 200cc D5W and infused over 30 minutes into right atrial catheter on days -5, -4, -3, -2.	Drug	BEAM Regimen
etoposideEtoposide administration 200 mg /m2 dissolved in 1 liter NS and infused over 2 hours into right atrial catheter. Infusion to begin after cytarabine administration on days -5, -4, -3, -2. Etoposide administration 50 mg/kg IV over 24 hours, divided into 3 doses. Dilute in normal saline at a concentration of 0.4 mg/ml (Observe for precipitation). Administered IV with continuous infusion over 24 hours. Diuretics may be given for fluid overload.	Drug	BEAM Regimen, Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only)
fludarabine phosphateFludarabine administered at 30 mg/m2 IVPB infused over 30 minutes into right atrial catheter on days -4, -3, -2. Fludarabine administered at 40 mg/m2 IVPB infused over 30 into the right atrial catheter on days -5, -4, -3, and -2.	Drug	Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Low-Dose Fludarabine and TBI(for second stem cell donation)
melphalan140 mg /m2 in concentration of 0.45 mg/ml of NS infused over 30 minutes into right atrial catheter on day -1.	Drug	BEAM Regimen
methotrexateAdministered on days +1, +3, and +7.	Drug	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
methylprednisoloneMethyl-prednisolone is administered IV as a rapid infusion.	Drug	ATG For Cord Blood Transplants
mycophenolate mofetilMycophenolate may be used as a substitute for Methotrexate	Drug	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
tacrolimusAlso: FK-506A drug used to decrease the risk of graft versus host disease (GvHD).	Drug	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
peripheral blood stem cell transplantationThe stem cells will be given to you by intravenous injection (through your vein) using a catheter that was placed prior to beginning chemotherapy. The stem cell infusion takes 1-6 hours.	Procedure or surgery	ATG For Cord Blood Transplants, BEAM Regimen, Busulfan and Cyclophosphamide (Cytoxan), Busulfan, Cyclophosphamide, and Fludarabine (Pediatric only), Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), DLI (Donor Leukocyte Infusion), Low-Dose Fludarabine and TBI(for second stem cell donation)
umbilical cord blood transplantationThe patient will receive ATG to improve the changes of engraftment and decrease their risk of graft versus host disease. The patient may receive ATG 3 times during their transplant regimen on days -3 through days -1	Procedure or surgery	ATG For Cord Blood Transplants
radiation therapyRadiation will be given to you 2 times a day for 3 or 4 days.	Radiation	Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI), Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric only), Low-Dose Fludarabine and TBI(for second stem cell donation)

Primary outcome

Number of Participants With Disease Free Survival (DFS).
Time frame: Duration of the study; Up to 2 years
Determine the effectiveness of unrelated donor allogeneic hematopoietic stem cells for transplantation after conditioning for the treatment of high-risk hematopoietic malignancies. Disease-free survival: The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer.

Results and safety

Results posted to the registry on 19 Jun 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI)	128	0
Busulfan and Cyclophosphamide (Cytoxan)	36	0
BEAM Regimen	20	0
Low-Dose Fludarabine and TBI(for Second Stem Cell Donation)	0	0
Busulfan, Cyclophosphamide, and Fludarabine (Pediatric Only)	6	0
ATG For Cord Blood Transplants	9	0
DLI (Donor Leukocyte Infusion)	0	0
Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric Only)	1	0

Primary outcome: Number of Participants With Disease Free Survival (DFS).

Time frame: Duration of the study; Up to 2 years

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cyclophosphamide (Cytoxan) and Total Body Irradiation (TBI)	101 of 128 (78.9%)	19 of 128 (14.8%)	Not reported
Busulfan and Cyclophosphamide (Cytoxan)	25 of 36 (69.4%)	0 of 36 (0%)	Not reported
BEAM Regimen	17 of 20 (85%)	2 of 20 (10%)	Not reported
Low-Dose Fludarabine and TBI(for Second Stem Cell Donation)	0 of 0	0 of 0	Not reported
Busulfan, Cyclophosphamide, and Fludarabine (Pediatric Only)	5 of 6 (83.3%)	0 of 6 (0%)	Not reported
ATG For Cord Blood Transplants	6 of 9 (66.7%)	0 of 9 (0%)	Not reported
DLI (Donor Leukocyte Infusion)	0 of 0	0 of 0	Not reported
Cyclophosphamide, Etoposide (VP16) and TBI (Pediatric Only)	1 of 1 (100%)	0 of 1 (0%)	Not reported

Limitations and caveats (from the sponsor): Early termination

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard Maziarz, MD study chair

OHSU Knight Cancer Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Disease Free Survival (DFS). (time frame: Duration of the study; Up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00281879.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2017.