Hematologic MalignanciesPhase 1/2NCT00506857
Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support
A Phase 1/2 study testing Busulfan and Fludarabine in people with Hematologic Malignancies, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Objectives: 1. To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludarabine and busulfan at different dose levels and different dose schedules in patients undergoing allogeneic stem cell transplant (SCT). 2. Read more about this study
- Who is it for?
- Ages Up to 75 years
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- Busulfan and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to Aug 2011
- Phase
- Phase 1/2
- 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 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Less than physiologic 75 years of age.
- Interferon resistant late chronic phase CML not eligible for a protocol of higher priority.
- Accelerated/Blastic Phase CML.
- Acute leukemia or Intermediate to High Risk MDS according to the IPPS.
- Any Lymphoma or Myeloma beyond CR1 ineligible for a protocol of higher priority.
- Patients must have an HLA compatible donor willing to donate either peripheral blood or bone marrow progenitor cells.
- Both patients and donor must sign written informed consents.
Who cannot join
- Uncontrolled infection
- Bilirubin >3.0
- Creatinine >2.5
- Performance Status >Zubrod 2
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies
Objectives:
- To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludarabine and busulfan at different dose levels and different dose schedules in patients undergoing allogeneic stem cell transplant (SCT).
- Determine pharmacokinetics, and toxicity of intravenous busulfan given at equal total dose levels given four times daily, or once daily.
- In vivo determination of fludarabine inhibitory effects on DNA repair.
Read the detailed description
Treatment: Participants will have blood tests and bone marrow tests as well as tests to check lung, heart, kidney, and liver functions. Participants will receive busulfan by vein for 2 to 4 days depending on their age and medical condition. All participants will receive fludarabine which will be given over 4 days. Participants undergoing unmatched or matched unrelated donors will receive ATG over 4 days to help with the engraftment of the donor progenitor cells. All drugs are given through the vein daily.
The donor blood cells will be taken from the donor through a process known as apheresis. This will occur after the donor has received 2 days of granulocyte colony stimulating factor (G-CSF) to increase her/his white cell count. The G-CSF will also increase the number of very immature (stem cells) that are to be collected. Apheresis is similar to a platelet donation, but white cells and stem cells are collected instead. About 3 to 5 apheresis procedures will be needed to get enough cells for infusion. If apheresis is not used, donor bone marrow will be taken under general anesthesia.
After the participants receives the donor stem cells, the stem cells divide and reconstitute bone marrow function, blood function, and immunity. The donor stem cells are given after the chemotherapy to shorten the period of low blood counts. They are also given at this time to achieve an antileukemic effect whereby the donor immune cells will recognize the participant's leukemia as "foreign" and prevent its recurrence. A small amount of donor cells will be kept for infusion on a future date (usually 3 and 6 months post transplant) to try to prevent the disease from coming back.
During the 4 to 8 weeks following blood cell infusion, participants will need frequent blood tests to monitor their counts and blood chemistries. Participants will need frequent blood transfusion and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to check response. Participants that achieve normal bone marrow and blood counts will be evaluated to determine the most appropriate form of future therapy. Participants who fail to respond to treatment will be offered other therapies.
This is an investigational study. All through all drugs are commercially available. Up to 140 participants will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.
- Conditions
- Hematologic Malignancies
- Being tested
- Busulfan, Fludarabine
- Keywords
- Hematologic Malignancies, Blood And Marrow Transplantation, Leukemia, MDS, Lymphoma, Myeloma, Fludarabine, Fludara, Fludarabine Phosphate, Busulfan, Busulfex, Myleran, Progenitor Cell Transplantation, Granulocyte colony stimulating factor, G-CSF, Apheresis, Blood cell infusion
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Lymphoma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called Busulfex, Myleran
Starting Dose 0.8 mg/kg by vein every 6 hours x 12 doses.
FludarabineDrug
Also called Fludarabine phosphate, Fludara
30 mg/m^2 by vein daily x 4 days.
| Study group | Role | What they receive |
|---|---|---|
| Busulfan + Fludarabine | Experimental | Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m^2 IV daily for 4 days. Receives: Drug: Busulfan; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity [National Cancer Institute Common Toxicity Criteria (NCI-CTC)]. Participant evaluation in a cohort with each modality is 30 days.
Measured: 1 month
Secondary outcomes (1)
Number of Participants With Graft Versus Host Disease (GVHD)
Tacrolimus and Methotrexate used for acute graft versus host disease (aGVHD) prophylaxis, clinical grading AGVHD criteria (Days 1-100): Grade 1: + to ++ skin rash; no gut involvement; no decrease in clinical performance status; Grade 2: + to +++ skin rash; + gut involvement and/or + liver involvement; mild decrease in performance status; Grade 3: ++ to +++ skin rash; ++ to +++ gut involvement and/or ++ to ++++ liver involvement; marked decrease in performance status; Grade 4: Similar to Grade 3 with ++ to ++++ organ involvement and extreme decrease in performance status.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2007 (estimated)
- Study startNov 2003
- Primary completionAug 2011
- Study completionAug 2011
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 Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard E. Champlin, MD, BS, Principal investigator, UT MD Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00506857
- Sponsor's protocol ID
- DM99-251
- Status last verified
- Jan 2012
- First submitted
- 23 Jul 2007
- Last updated
- 28 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT00506857
- Acronym / sponsor ID
- DM99-251
- Conditions
- Hematologic Malignancies
- Keywords
- Hematologic Malignancies, Blood And Marrow Transplantation, Leukemia, MDS, Lymphoma, Myeloma, Fludarabine, Fludara
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Nov 2003
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 25 Jul 2007 (estimated)
- Results
- Posted 28 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives:
- To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludarabine and busulfan at different dose levels and different dose schedules in patients undergoing allogeneic stem cell transplant (SCT).
- Determine pharmacokinetics, and toxicity of intravenous busulfan given at equal total dose levels given four times daily, or once daily.
- In vivo determination of fludarabine inhibitory effects on DNA repair.
Detailed description
Treatment: Participants will have blood tests and bone marrow tests as well as tests to check lung, heart, kidney, and liver functions. Participants will receive busulfan by vein for 2 to 4 days depending on their age and medical condition. All participants will receive fludarabine which will be given over 4 days. Participants undergoing unmatched or matched unrelated donors will receive ATG over 4 days to help with the engraftment of the donor progenitor cells. All drugs are given through the vein daily.
The donor blood cells will be taken from the donor through a process known as apheresis. This will occur after the donor has received 2 days of granulocyte colony stimulating factor (G-CSF) to increase her/his white cell count. The G-CSF will also increase the number of very immature (stem cells) that are to be collected. Apheresis is similar to a platelet donation, but white cells and stem cells are collected instead. About 3 to 5 apheresis procedures will be needed to get enough cells for infusion. If apheresis is not used, donor bone marrow will be taken under general anesthesia.
After the participants receives the donor stem cells, the stem cells divide and reconstitute bone marrow function, blood function, and immunity. The donor stem cells are given after the chemotherapy to shorten the period of low blood counts. They are also given at this time to achieve an antileukemic effect whereby the donor immune cells will recognize the participant's leukemia as "foreign" and prevent its recurrence. A small amount of donor cells will be kept for infusion on a future date (usually 3 and 6 months post transplant) to try to prevent the disease from coming back.
During the 4 to 8 weeks following blood cell infusion, participants will need frequent blood tests to monitor their counts and blood chemistries. Participants will need frequent blood transfusion and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to check response. Participants that achieve normal bone marrow and blood counts will be evaluated to determine the most appropriate form of future therapy. Participants who fail to respond to treatment will be offered other therapies.
This is an investigational study. All through all drugs are commercially available. Up to 140 participants will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Busulfan + Fludarabine | Experimental | Drug: Busulfan, Drug: FludarabineBusulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m^2 IV daily for 4 days. |
Who may qualify
- Ages
- Up to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Less than physiologic 75 years of age.
- Interferon resistant late chronic phase CML not eligible for a protocol of higher priority.
- Accelerated/Blastic Phase CML.
- Acute leukemia or Intermediate to High Risk MDS according to the IPPS.
- Any Lymphoma or Myeloma beyond CR1 ineligible for a protocol of higher priority.
Key exclusion criteria (4 listed)
- Uncontrolled infection
- Bilirubin >3.0
- Creatinine >2.5
- Performance Status >Zubrod 2
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 |
|---|---|---|
| BusulfanAlso: Busulfex, MyleranStarting Dose 0.8 mg/kg by vein every 6 hours x 12 doses. | Drug | Busulfan + Fludarabine |
| FludarabineAlso: Fludarabine phosphate, Fludara30 mg/m^2 by vein daily x 4 days. | Drug | Busulfan + Fludarabine |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 1 month
Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity [National Cancer Institute Common Toxicity Criteria (NCI-CTC)]. Participant evaluation in a cohort with each modality is 30 days.
1 secondary outcome
Number of Participants With Graft Versus Host Disease (GVHD)
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
Related trials for Hematologic Malignancies
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
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 E. Champlin, MD, BS principal investigator
UT MD Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Busulfan and Fludarabine in people with Hematologic Malignancies, run by M.D. Anderson Cancer Center 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?
The sponsor lists 7 inclusion and 4 exclusion criteria. 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 28 Feb 2012. 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 combined 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.
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 28 Feb 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?
Maximum Tolerated Dose (MTD) (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Feb 2012.