AzTrials
AzTrials

Chronic Myeloproliferative DisordersPhase 2NCT00134017

Combination Chemotherapy, Bone Marrow Transplant, and Post Transplant Cyclophosphamide for Hematologic Cancer

A Phase 2 study testing Busulfan and Cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. Read more about this study

Who is it for?
Ages 6 months to 65 years
What is being tested?
Busulfan and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
142 participants
Where
1 siteUnited States
Study dates
Jun 2004to Feb 2010
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 6 months to 65 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following hematologic malignancies:
  • Acute myeloid leukemia (AML), meeting 1 of the following criteria:
  • AML beyond first complete remission (CR1)
  • Refractory AML
  • AML arising from myelodysplastic syndromes (MDS)
  • Secondary AML
  • MDS
  • Refractory anemia with excess blasts with > 10% blasts in bone marrow
  • Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:
  • ALL in CR1 with 1 of the following high-risk features:
  • Philadelphia chromosome (Ph)-positive disease
  • Less than 1 year of age at diagnosis
  • Cytogenetic abnormalities involving chromosome 11q23
  • ALL beyond CR1
  • Refractory ALL
  • Chronic myeloid leukemia beyond first chronic phase
  • Chronic myelomonocytic leukemia
  • Chronic lymphocytic leukemia
  • Stage III-IV disease
  • Does not meet criteria for other bone marrow transplantation (BMT) studies
  • Myeloproliferative disorders
  • Ph-negative disease
  • Hodgkin's or non-Hodgkin's lymphoma
  • Chemotherapy-resistant disease
  • Paroxysmal nocturnal hemoglobinuria with life-threatening thrombosis
  • Multiple myeloma
  • Stage II or III disease
  • Very high-risk disease
  • Having an unrelated donor is considered a high-risk condition
  • Meets medical criteria for myeloablative BMT for the Sidney Kimmel Comprehensive Cancer Center
  • Bone marrow donor available, meeting 1 of the following criteria:
  • Genotypically HLA-identical sibling
  • Phenotypically matched first-degree relative
  • Unrelated donor molecularly matched at HLA-A, -B, -C, -DRB1, and -DQB1

PATIENT CHARACTERISTICS:

Age

  • 6 months to 65 years

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • No concurrent dexamethasone as an antiemetic during immunosuppression therapy

Radiotherapy

  • Not specified

Surgery

  • Not specified

Other

  • No concurrent immunosuppressants until ≥ 24 hours after the completion of cyclophosphamide (post-transplantation)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: HLA Matched Related and Unrelated Bone Marrow Transplantation With Busulfan/Cyclophosphamide and Post Transplantation Cyclophosphamide for Hematological Malignancies

RATIONALE: Giving chemotherapy before a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclophosphamide, mycophenolate mofetil, or tacrolimus after transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving combination chemotherapy together with tacrolimus and mycophenolate mofetil works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.

Read the detailed description

OBJECTIVES:

Primary

  • Determine the optimal dose of post-transplant immunosuppression comprising high-dose cyclophosphamide, tacrolimus, and mycophenolate mofetil administered after myeloablative conditioning chemotherapy comprising busulfan and cyclophosphamide followed by allogeneic bone marrow transplantation in patients with high-risk hematologic malignancies.
  • Determine the incidence and severity of acute graft-versus-host disease in patients treated with this regimen.
  • Determine other toxic effects of this regimen in these patients.

Secondary

  • Determine immune reconstitution in patients treated with this regimen.
  • Determine disease control in patients treated with this regimen.

OUTLINE: This is a pilot study. Patients are stratified according to age (≤ 19 years old vs > 19 years old).

  • Myeloablative conditioning chemotherapy: Patients receive busulfan IV or orally 4 times daily on days -7 to -4 OR days -6 to -3 and cyclophosphamide IV over 1 hour once daily on days -3 to -1 OR days -2 and -1.
  • Allogeneic bone marrow transplantation: Patients undergo allogeneic bone marrow transplantation on day 0.
  • Immunosuppression therapy: Patients receive high-dose cyclophosphamide IV over 1 hour on days 3 and 4.

After completion of study transplantation, patients are followed at 30 and 60 days, 6 months, 1 year, and then annually thereafter.

Keywords
adult acute myeloid leukemia in remission, refractory anemia with excess blasts, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, 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), childhood acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia
Medical subject headings
Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Congenital Abnormalities

What participants receive

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

  • BusulfanDrug

    Also called Myleran, Busulfex

    Days -7 to -4: 4 mg/kg PO daily OR 3.2 mg/kg IV daily OR 160 mg/m^2 daily (for pediatric recipients)

  • CyclophosphamideDrug

    Also called Cytoxan, CTX

    Days -3, -2, +3, +4: 50 mg/kg IV daily

Study groups in NCT00134017
Study groupRoleWhat they receive
Bone marrow transplantExperimentalMyeloablative bone marrow transplant with a busulfan (Bu), cyclophosphamide (Cy), preparative regimen and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis
Receives: Drug: Busulfan; Drug: Cyclophosphamide

What is being measured

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

  1. Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD)

    Percentage of participants who developed grades II-IV and grades III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).

    Measured: Day 100

Secondary outcomes (4)

  1. Days to Engraftment

    Median number of days to neutrophil and platelet engraftment.

    Measured: Up to one year

  2. Chimerism

    Number of patients who achieved 100% donor chimerism.

    Measured: Day 30, Day 60

  3. Non-relapse Mortality

    Percentage of participants who died for BMT-related reasons.

    Measured: Day 100, 2 years

  4. Relapse

    Percentage of participants who developed relapse or progressive disease.

    Measured: 2 years

Timeline

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

  1. First posted24 Aug 2005 (estimated)
  2. Study startJun 2004
  3. Primary completionFeb 2010
  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
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00134017
Sponsor's protocol ID
J0373
Other IDs
P01CA015396, P30CA006973, NA_00034100
Status last verified
Aug 2018
First submitted
22 Aug 2005
Last updated
31 Aug 2018
Individual data sharing
No

Publications

  • Luznik L, Bolanos-Meade J, Zahurak M, Chen AR, Smith BD, Brodsky R, Huff CA, Borrello I, Matsui W, Powell JD, Kasamon Y, Goodman SN, Hess A, Levitsky HI, Ambinder RF, Jones RJ, Fuchs EJ. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-30. doi: 10.1182/blood-2009-11-251595. Epub 2010 Feb 2.

    PubMed 20124511

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan and Cyclophosphamide in people with Chronic Myeloproliferative Disorders and Leukemia, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

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: finished, as of the sponsor's last update on 31 Aug 2018. 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 31 Aug 2018). 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?

Percentage of Participants Who Develop Acute Graft-versus-host Disease (GVHD) (time frame: Day 100). 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 NCT00134017, which also lists 1 linked publication.

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 31 Aug 2018.

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