Chronic Myeloproliferative DisordersPhase 1NCT00800150

Total Marrow and Total Lymph Node Irradiation, Fludarabine, and Melphalan Followed By Donor Stem Cell Transplant in Treating Patients With Advanced Hematological Cancer That Has Not Responded to Treatment

A Phase 1 study testing fludarabine phosphate, melphalan and nonmyeloablative allogeneic hematopoietic stem cell transplantation in people with Chronic Myeloproliferative Disorders and Leukemia, run by City of Hope Medical Center 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

RATIONALE: Giving total marrow and total lymph node irradiation together with low doses of chemotherapy before a donor stem cell 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?: Ages 16 years and older
Conditions the study is for: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma
What is being tested?: fludarabine phosphate, melphalan and nonmyeloablative allogeneic hematopoietic stem cell transplantation
Type of treatment: Surgery or procedure
How many people: 6 participants
Where: 1 siteUnited States
Study dates: Nov 2008to Oct 2010
Phase: Phase 1
Are there results?: None posted in the registry

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 16 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

DISEASE CHARACTERISTICS:

Histopathologically confirmed diagnosis of 1 of the following:
Acute myeloid leukemia (AML)
Myelodysplastic syndromes
Intermediate- or high-risk disease
Myelofibrosis
Granulocytic sarcoma (chloroma)
With or without bone marrow involvement
Mixed lineage leukemia
Induction therapy must have been directed predominantly against AML
Acute lymphoblastic leukemia
Non-Hodgkin lymphoma
Multiple myeloma
Relapsed or refractory disease with M3 marrow (marrow blasts > 25%), meeting 1 of the following criteria:
Persistent disease after an induction attempt
Persistent initial disease after two induction attempts
Relapse after one re-induction attempt (second relapse)
Persistent disease after first relapse and initial re-induction attempt
Not eligible for myeloablative allogeneic hematopoietic stem cell transplantation due to age (> 50 years), organ insufficiency, or significant comorbidity
Patients 16-50 years of age must meet ≥ 1 of the following criteria:
Ejection fraction 50-60% by MUGA scan and/or echocardiogram
DLCO 50-75% of predicted
Creatinine clearance or GFR 60-80 mL/min
Serum bilirubin ≤ 2.0 mg/dL
SGOT and SGPT 1.5-5 times upper limit of normal
No other medical and/or psychosocial problem that, in the opinion of the primary physician or principal investigator, would place the patient at unacceptable risk from study regimen
No Fanconi anemia
HLA-identical sibling OR matched unrelated donor available

PATIENT CHARACTERISTICS:

Zubrod or Karnofsky performance status 70-100%
Negative pregnancy test
Able to lie supine in a full body cast for 30 minutes
No HIV infection
No evidence of active hepatitis B or C infection
No evidence of cirrhosis
No uncontrolled viral, bacterial, or fungal infection within the past 4 weeks
No radiographic changes indicating pulmonary disease (e.g., pulmonary nodules, infiltrates, or pleural effusion) unless cleared by pulmonary biopsy that shows no evidence of active pulmonary disease
No major medical or psychiatric disorder that would seriously compromise patient tolerance of study regimen

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior radiation therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000

Other trials in United States

About this study

Official title: Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen

PURPOSE: This phase I trial is studying the side effects and best dose of total marrow and total lymph node irradiation when given together with fludarabine and melphalan followed by donor stem cell transplant in treating patients with advanced hematological cancer that has not responded to treatment.

Read the detailed description

OBJECTIVES:

Primary

To determine the maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation (TMLI) using helical tomotherapy in combination with a reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in patients undergoing allogeneic hematopoietic stem cell transplantation for advanced, relapsed or refractory hematological malignancies.
To describe the toxicities of escalating doses of TMLI in these patients.

Secondary

To describe the frequency of clinical response in patients treated with this regimen.
To describe the frequency of primary and secondary engraftment failure in patients treated with this regimen.
To describe the time to neutrophil and platelet engraftment in patients treated with this regimen.
To describe the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
To describe the overall survival of patients treated with this regimen.
To describe the progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node irradiation (TMLI).

Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow, major lymph node chains, spleen, and liver using helical tomotherapy twice daily on days -6 to -3.
Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and melphalan IV on day -1.
Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.

After completion of study treatment, patients are followed periodically.

Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Being tested: fludarabine phosphate, melphalan, nonmyeloablative allogeneic hematopoietic stem cell transplantation, intensity-modulated radiation therapy, tomotherapy
Keywords: 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), recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult T-cell leukemia/lymphoma, secondary acute myeloid leukemia, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, adult grade III lymphomatoid granulomatosis, adult nasal type extranodal NK/T-cell lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, splenic marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma
Medical subject headings: Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma, Neoplasms, Plasma Cell, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Congenital Abnormalities

What participants receive

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

fludarabine phosphateDrug
melphalanDrug
nonmyeloablative allogeneic hematopoietic stem cell transplantationProcedure or surgery
intensity-modulated radiation therapyRadiation
tomotherapyRadiation
total marrow irradiationRadiation
total nodal irradiationRadiation

What is being measured

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

Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy
Toxicity

Secondary outcomes (6)

Frequency of clinical response
Frequency of primary and secondary engraftment failure
Time to neutrophil and platelet engraftment
Incidence of acute and chronic graft-versus-host disease
Overall survival
Progression-free survival

Timeline

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

Nov 2008Oct 2010

First posted1 Dec 2008 (estimated)
Study startNov 2008
Primary completionOct 2010
Study completionOct 2010

Why it stopped: Protocol objective could not be met. A new study with amended eligibility criteria will be developed.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Myeloproliferative DisordersStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe 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 1
Primary purpose: Treatment
Enrolment: 6 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00800150
Sponsor's protocol ID: 08076
Other IDs: P30CA033572, CHNMC-08076, CDR0000626148
Status last verified: Jun 2015
First submitted: 27 Nov 2008
Last updated: 8 Jun 2015
Results posted: No
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

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All Chronic Myeloproliferative Disorders trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study of Escalating Doses of Radiation Therapy Using Helical Tomotherapy in Combination With Fludarabine (FLU) and Melphalan (MEL) as a Preparative Regimen for Allogeneic Hematopoietic Stem Cell (HSC) Transplantation in Patients With Advanced and Hematological Malignancies Who Are Not Eligible for Fully Myeloablative Regimen
ClinicalTrials.gov ID: NCT00800150
Acronym / sponsor ID: 08076
Conditions: Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords: 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), recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult T-cell leukemia/lymphoma
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Protocol objective could not be met. A new study with amended eligibility criteria will be developed.
Enrolment: 6 participants (actual)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: Nov 2008
Primary completion: Oct 2010 (actual)
Study completion: Oct 2010 (actual)
First posted: 1 Dec 2008 (estimated)
Results: Not posted in the source record

Clinical summary

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

Detailed description

OBJECTIVES:

Primary

To determine the maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation (TMLI) using helical tomotherapy in combination with a reduced-intensity preparative regimen comprising fludarabine phosphate and melphalan in patients undergoing allogeneic hematopoietic stem cell transplantation for advanced, relapsed or refractory hematological malignancies.
To describe the toxicities of escalating doses of TMLI in these patients.

Secondary

To describe the frequency of clinical response in patients treated with this regimen.
To describe the frequency of primary and secondary engraftment failure in patients treated with this regimen.
To describe the time to neutrophil and platelet engraftment in patients treated with this regimen.
To describe the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
To describe the overall survival of patients treated with this regimen.
To describe the progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of intensity-modulated total marrow and lymph node irradiation (TMLI).

Intensity-modulated radiation therapy: Patients undergo TMLI to skeletal bone/marrow, major lymph node chains, spleen, and liver using helical tomotherapy twice daily on days -6 to -3.
Reduced-intensity preparative regimen: Patients receive fludarabine phosphate IV on days -6 to -2 and melphalan IV on day -1.
Hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.

After completion of study treatment, patients are followed periodically.

Study design

Primary purpose: Treatment

Who may qualify

Ages: 16 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older 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
fludarabine phosphate	Drug	–
melphalan	Drug	–
nonmyeloablative allogeneic hematopoietic stem cell transplantation	Procedure or surgery	–
intensity-modulated radiation therapy	Radiation	–
tomotherapy	Radiation	–
total marrow irradiation	Radiation	–
total nodal irradiation	Radiation	–

Primary outcome

Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy
Toxicity

6 secondary outcomes

Frequency of clinical response
Frequency of primary and secondary engraftment failure
Time to neutrophil and platelet engraftment
Incidence of acute and chronic graft-versus-host disease
Overall survival
Progression-free survival

Results and safety

The study was stopped early (reason given: Protocol objective could not be met. A new study with amended eligibility criteria will be developed.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2015.

Related trials for Chronic Myeloproliferative Disorders

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Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
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RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
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RecruitingObservational study
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Chronic Myeloid Leukemia
RecruitingPhase 1
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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.

Joseph Rosenthal, MD principal investigator

City of Hope Medical Center

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 8 Jun 2015. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: Protocol objective could not be met. A new study with amended eligibility criteria will be developed.). Results are not available in the source record.

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?

Maximum tolerated dose of intensity-modulated total marrow and lymph node irradiation using helical tomotherapy. The study lists 2 primary outcomes in all. 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 NCT00800150.

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 8 Jun 2015.