Chemotherapy + Stem Cell Transplant for Blood Cancers

Recruiting in Palo Alto (17 mi)

Uday R Popat | MD Anderson Cancer Center

Overseen byUday R. Popat

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Trial Summary

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.

Eligibility Criteria

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.

+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.

+4 more

Participant Groups

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.

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: