Stem Cell Transplant + Chemotherapy for Leukemia and Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Roswell Park Cancer Institute

Disqualifiers: Myelofibrosis, HLA antibodies, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, 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 and total-body irradiation 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. 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 (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications. It mentions a washout period for prior chemotherapy, but other medications are at the physician's discretion.

What data supports the effectiveness of the treatment involving stem cell transplant, chemotherapy, and total-body irradiation for leukemia and lymphoma?

Research shows that using total-body irradiation (TBI) with chemotherapy drugs like cyclophosphamide and fludarabine can be effective in treating leukemia and lymphoma. For example, a study found that a regimen including TBI and fludarabine resulted in a lower risk of non-relapse mortality compared to other regimens, suggesting it may be a safer option for some patients. ^{1 2 3 4 5}

Is the treatment of stem cell transplant with chemotherapy for leukemia and lymphoma generally safe in humans?

A study on mycophenolate mofetil, a drug used in this treatment, showed it is safe for kidney transplant patients, suggesting it may be safe for other uses too. Additionally, a study involving sirolimus, another drug in this treatment, found it safe when used with other medications for cancer patients. ^{6 7 8 9 10}

How does the stem cell transplant and chemotherapy treatment for leukemia and lymphoma differ from other treatments?

This treatment combines stem cell transplant with chemotherapy, which is unique because it uses high-dose chemotherapy to destroy cancer cells and then replaces damaged blood-forming cells with healthy stem cells. This approach can be more effective in reducing relapse rates compared to chemotherapy alone, as it allows for higher doses of chemotherapy to be used safely. ^{5 11 12 13 14}

Research Team

Maureen Ross

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients with various blood cancers or bone marrow disorders who have a compatible donor for stem cell transplant. They should be in certain disease states, like remission or very good partial response, and have adequate organ function. Participants must not be HIV positive, pregnant, nursing, or have severe myelofibrosis; they need to understand the study and agree to use birth control.

Inclusion Criteria

My leukemia is in partial remission, or my multiple myeloma is responding well to treatment.

Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately

I am able to care for myself but cannot do normal activities or work.

Exclusion Criteria

Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Your doctor thinks you may have a hard time following the rules for stem cell transplantation due to serious mental health issues or difficult social circumstances.

I am HIV positive.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Participants receive fludarabine phosphate and melphalan hydrochloride, followed by total body irradiation

5 days

Daily visits for 5 days

Stem Cell Infusion

Participants undergo allogeneic hematopoietic stem cell transplant

1 day

1 visit (in-person)

GVHD Prophylaxis Regimen

Participants receive cyclophosphamide, mycophenolate mofetil, and tacrolimus to prevent graft versus host disease

180 days

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Annual visits

Treatment Details

Interventions

• Cyclophosphamide
• Fludarabine Phosphate
• Melphalan Hydrochloride
• Mycophenolate Mofetil
• Sirolimus
• Total-Body Irradiation

Trial Overview The trial tests if chemotherapy combined with total body irradiation and post-transplant cyclophosphamide can reduce graft versus host disease after a donor stem cell transplant. It includes drugs like fludarabine phosphate and melphalan hydrochloride that stop cancer cells from growing.

Participant Groups

Group I: Prevention (chemotherapy, TBI, cyclophosphamide) Experimental Treatment 8 Interventions

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Findings from Research

In a study of 146 adults with acute lymphoblastic leukemia undergoing transplantation, both conditioning regimens (Cyclophosphamide/Total Body Irradiation vs. Fludarabine/Busulfan/Low-dose TBI) showed similar overall and progression-free survival rates, indicating comparable efficacy.

However, the Fludarabine/Busulfan/Low-dose TBI regimen resulted in a significantly lower relapse rate (18.5% vs. 31.5% for Cy/TBI), suggesting it may be a safer option, especially for patients with poorer performance status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, busulfan, and low-dose TBI conditioning versus cyclophosphamide and TBI in allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. Speziali, C., Daly, A., Abuhaleeqa, M., et al.[2020]

In a study of 2,255 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation, conditioning with total body irradiation (TBI) plus cyclophosphamide (Cy) significantly reduced the risk of relapse compared to TBI plus fludarabine (Flu), with a relapse rate of 18% versus 30% at 2 years.

While TBI/Cy was associated with a higher risk of grade 2-4 acute graft-versus-host disease (GVHD), it did not significantly affect other transplantation outcomes, suggesting that TBI/Cy may be a preferable conditioning regimen for patients in complete remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT. Giebel, S., Labopin, M., Socié, G., et al.[2023]

Recent studies on pretransplant conditioning regimens for acute myelogenous leukemia (AML) show mixed results, with some new regimens reducing leukemia relapse but not improving overall leukemia-free survival due to increased mortality from non-leukemia causes.

A subset of new regimens demonstrated improved antileukemia efficacy and leukemia-free survival, but their benefits were not significantly better than traditional treatments like cyclophosphamide and total body radiation, suggesting potential limitations in current clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are new conditioning regimens for transplants in acute myelogenous leukemia better? Aurer, I., Gale, RP.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fludarabine, busulfan, and low-dose TBI conditioning versus cyclophosphamide and TBI in allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Combined modality therapy for advanced, diffuse lymphocytic and histiocytic lymphomas. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation following a busulfan-based conditioning regimen in young children with acute lymphoblastic leukemia: a Cooperative Study of the Société Française de Greffe de Moelle. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Total body irradiation plus fludarabine versus thiotepa, busulfan plus fludarabine as a myeloablative conditioning for adults with acute lymphoblastic leukemia treated with haploidentical hematopoietic cell transplantation. A study by the Acute Leukemia Working Party of the EBMT. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma. [2017]

6. Spain pubmed.ncbi.nlm.nih.gov

Gateways to clinical trials. [2007]

7. United States pubmed.ncbi.nlm.nih.gov

Pilot study on the efficacy and safety of generic mycophenolate mofetil (Mycept) compared with Cellcept among incident low-risk primary kidney transplant recipients. [2016]

8. England pubmed.ncbi.nlm.nih.gov

A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Triplet chemotherapy in combination with anti-EGFR agents for the treatment of metastatic colorectal cancer: Current evidence, advances, and future perspectives. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

High-dose cyclophosphamide and rituximab without stem cell transplant: a feasibility study for low grade B-cell, transformed and mantle cell lymphomas. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Outcome of Patients With Non-Hodgkin Lymphomas With Concurrent MYC and BCL2 Rearrangements Treated With CODOX-M/IVAC With Rituximab Followed by Hematopoietic Stem Cell Transplantation. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Are new conditioning regimens for transplants in acute myelogenous leukemia better? [2019]