204 Participants Needed

Chemotherapy + Stem Cell Transplant for Blood Cancers

Age: Any Age
Sex: Any
Trial Phase: Phase 2
Sponsor: M.D. Anderson Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies the side effect of busulfan, fludarabine phosphate, and post-transplant cyclophosphamide in treating patients with blood cancer undergoing donor stem cell transplant. Drugs used in chemotherapy, such as busulfan, fludarabine phosphate and cyclophosphamide work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy such as busulfan and fludarabine phosphate before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving cyclophosphamide after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does the chemotherapy and stem cell transplant treatment with Busulfan and Fludarabine differ from other treatments for blood cancers?

This treatment combines Busulfan and Fludarabine, which is unique because it offers similar effectiveness to the traditional Busulfan and Cyclophosphamide regimen but with less toxicity, making it a potentially safer option for patients undergoing stem cell transplants for blood cancers.12345

What data supports the effectiveness of the treatment involving Busulfan, Cyclophosphamide, and Fludarabine Phosphate for blood cancers?

Research shows that using Busulfan with Fludarabine or Cyclophosphamide in stem cell transplants can be effective for blood cancers like leukemia, with studies indicating good survival rates and manageable side effects. For example, one study found that a combination of Fludarabine and Busulfan resulted in a 71% overall survival rate in leukemia patients.12567

Who Is on the Research Team?

Uday R Popat | MD Anderson Cancer Center

Uday R. Popat

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with high-risk blood cancers like various leukemias, lymphomas, and myeloma. They should have a poor prognosis without transplant therapy and can be in remission or relapsed. Participants need functioning major organs, no active hepatitis B/C or HIV, not pregnant nor breastfeeding, willing to use contraception if applicable, and must have a suitable donor for stem cell transplant.

Inclusion Criteria

My heart pumps blood well.
My lung function tests are within normal limits, or if I'm a child under 7, my oxygen level is 92% or higher on room air.
My kidneys are functioning well enough to filter waste.
See 7 more

Exclusion Criteria

I have previously been treated with inotuzumab or gemtuzumab.
I am HIV positive.
I have had heart disease related to my arteries.
See 4 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Transplantation

Patients receive busulfan, fludarabine phosphate, and cyclophosphamide, followed by stem cell transplantation

Approximately 3 weeks
Multiple visits for chemotherapy administration and transplantation

Post-Transplantation Treatment

Patients receive cyclophosphamide and immunosuppressive therapy with tacrolimus and mycophenolate mofetil

Up to 3 months
Regular visits for monitoring and medication administration

Follow-up

Participants are monitored for safety, effectiveness, and incidence of graft versus host disease

Up to 3 years
Periodic visits for long-term monitoring

What Are the Treatments Tested in This Trial?

Interventions

  • Busulfan
  • Cyclophosphamide
  • Fludarabine Phosphate
Trial Overview The study tests busulfan and fludarabine phosphate chemotherapy followed by donor stem cell transplant with post-transplant cyclophosphamide treatment. It aims to see how well these drugs work together to stop cancer growth by killing cells or preventing their spread while reducing the risk of graft-versus-host disease.
How Is the Trial Designed?
6Treatment groups
Experimental Treatment
Group I: Group VI (matched or haploidentical transplant, chemotherapy)Experimental Treatment10 Interventions
Patients receiving fully matched or haploidentical donor transplant receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, a lower dose of thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.
Group II: Group V (haploidentical donor transplant, chemotherapy)Experimental Treatment10 Interventions
Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, a lower dose of thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.
Group III: Group IV (matched donor transplant, chemotherapy)Experimental Treatment8 Interventions
Patients receiving haploidentical related donor transplant, diagnosis of myelofibrosis, \> 60 years old, or patients with comorbidity scores \> 3 will go in Group 3 or 4. If patients with comorbidity score \>3, then the principal investigator is the final arbiter of eligibility for comorbidity score \> 3. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -20 and day -13) system exposure of 20,000 +/- 12% uMol-min based on the pharmacokinetic studies.
Group IV: Group III (haploidentical donor transplant, chemotherapy)Experimental Treatment10 Interventions
Patients receiving haploidentical related donor transplant, diagnosis of myelofibrosis, \> 60 years old, or patients with comorbidity scores \> 3 will go in Group 3 or 4. If patients with comorbidity score \> 3, then the principal investigator is the final arbiter of eligibility for comorbidity score \> 3. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -20 and day -13) system exposure of 20,000 +/- 12% uMol-min based on the pharmacokinetic studies.
Group V: Group II (matched donor transplant, chemotherapy)Experimental Treatment8 Interventions
Patients receive busulfan IV over 3 hours on days -13, -12, and -6 to -3, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months.
Group VI: Group I (haploidentical donor transplant, chemotherapy)Experimental Treatment10 Interventions
Patients receive busulfan IV over 3 hours on days -13, -12, and -6 to -3, thiotepa IV over 4 hours on day -7, fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo stem cell transplantation IV on day 0. Patients then receive cyclophosphamide IV over 3 hours on days 3 and 4. Beginning on day 5, patients receive tacrolimus IV continuously or PO BID for up to 3 months and mycophenolate mofetil PO TID.

Busulfan is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸
Approved in United States as Busulfex for:
  • Chronic myeloid leukemia
  • Acute myeloid leukemia
  • Malignant lymphoma
  • Bone marrow transplantation conditioning
🇪🇺
Approved in European Union as Busulfan for:
  • Chronic myeloid leukemia
  • Acute myeloid leukemia
  • Bone marrow transplantation conditioning
🇨🇦
Approved in Canada as Busulfex for:
  • Chronic myeloid leukemia
  • Acute myeloid leukemia
  • Bone marrow transplantation conditioning
🇯🇵
Approved in Japan as Busulfan for:
  • Chronic myeloid leukemia
  • Acute myeloid leukemia
  • Bone marrow transplantation conditioning

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

In a study of 32 patients with acute myeloid leukemia in first complete remission, the busulfan/fludarabine (Bu/Flu) conditioning regimen resulted in significantly lower transplant-related toxicity compared to the busulfan/cyclophosphamide (Bu/Cy) regimen, with a lower incidence of severe side effects (68.8% vs. 25.0%).
Both regimens showed similar efficacy in terms of overall survival and event-free survival rates, indicating that Bu/Flu is a safer option without compromising treatment effectiveness.
[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia].Liu, H., Fan, ZP., Jiang, QL., et al.[2014]
In a study of 62 patients undergoing reduced-intensity conditioning for stem cell transplantation, therapeutic dose monitoring of oral busulfan did not significantly impact post-transplant outcomes compared to standard dosing.
The presence of chronic graft-versus-host disease was identified as a strong predictor of overall survival and leukemia-free survival, highlighting its importance in patient outcomes after transplantation.
Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning.Martino, R., Pérez-Simón, JA., Moreno, E., et al.[2013]
In a study of 415 adult patients with relapsed and refractory non-Hodgkin lymphoma, those receiving the reduced-intensity conditioning regimen (Flu/Bu2) had a significantly better 5-year overall survival rate of 50.6% compared to 32.2% for those receiving the myeloablative regimen (Flu/Bu4).
The higher nonrelapse mortality (NRM) rate in the Flu/Bu4 group (31.9%) compared to the Flu/Bu2 group (15.7%) contributed to the poorer overall survival, indicating that the choice of conditioning regimen is critical for patient outcomes.
Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation.Kamijo, K., Shimomura, Y., Shinohara, A., et al.[2023]

Citations

[The efficacy and safety of modified busulfan/fludarabine conditioning regimen in elderly or drug-intolerable patients with hematologic malignancies]. [2014]
[A comparison of toxicity and efficacy between busulfan plus fludarabine and busulfan plus cyclophosphamide for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia]. [2014]
Reduced-intensity conditioning allogeneic blood stem cell transplantation with fludarabine and oral busulfan with or without pharmacokinetically targeted busulfan dosing in patients with myeloid leukemia ineligible for conventional conditioning. [2013]
Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation. [2023]
Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients. [2013]
Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. [2014]
F-ara-A pharmacokinetics during reduced-intensity conditioning therapy with fludarabine and busulfan. [2013]
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