44 Participants Needed

Inotuzumab Ozogamicin + Chemotherapy for Leukemia or Lymphoma

IF
Overseen ByIssa F Khouri
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

Trial Summary

What is the purpose of this trial?

The goal of this phase II clinical study is to learn about the safety of inotuzumab ozogamicin when given with fludarabine, with or without bendamustine, melphalan, and rituximab before and after a stem cell transplant. Researchers also want to learn if inotuzumab ozogamicin when given after a stem cell transplant can help control leukemia and lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab attaches to CD22-positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving chemotherapy before a bone marrow or peripheral blood 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 attack the body's normal cells (called graft-versus-host disease). Giving tacrolimus and filgrastim before or after the transplant may stop this from happening. Fludarabine, bendamustine, melphalan, and rituximab are commonly given before stem cell transplants. Giving inotuzumab ozogamicin with chemotherapy may work better in treating patients with leukemia or lymphoma undergoing stem cell transplantation.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, certain medications like rituximab, ibrutinib, and venetoclax are allowed shortly before starting the trial treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Bendamustine in treating leukemia or lymphoma?

Bendamustine has been shown to be effective in treating chronic lymphocytic leukemia and non-Hodgkin's lymphoma, with studies indicating it can improve progression-free survival and overall response rates in these conditions.12345

Is the combination of Inotuzumab Ozogamicin and Chemotherapy safe for treating leukemia or lymphoma?

Bendamustine, a component of the treatment, has been studied for safety in various blood cancers like chronic lymphocytic leukemia and non-Hodgkin's lymphoma. It is generally considered safe, with known side effects that can often be managed by adjusting the dose. Long-term safety data have been collected to ensure its safe use in patients.12346

What makes the drug combination of Inotuzumab Ozogamicin, Bendamustine, and Melphalan unique for treating leukemia or lymphoma?

This drug combination is unique because it combines Inotuzumab Ozogamicin, a targeted therapy that delivers a toxic agent directly to cancer cells, with Bendamustine and Melphalan, which are chemotherapeutic agents that work through different mechanisms to kill cancer cells. This multi-faceted approach may offer a novel treatment option for patients with leukemia or lymphoma, especially those who have not responded to standard therapies.13789

Research Team

IF

Issa F. Khouri

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults aged 18-35 with CD22+ lymphoid malignancies, including B-ALL, who are eligible for a reduced-intensity stem cell transplant. Participants must have proper liver and kidney function, not be pregnant or breastfeeding, and have a compatible donor. Excluded are those with high peripheral blast counts, certain heart conditions, HIV, active hepatitis B or C, recent chemotherapy or radiation treatments (with some exceptions), prior inotuzumab ozogamicin treatment within 3 weeks of study entry.

Inclusion Criteria

Negative beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization) or currently breast-feeding. Pregnancy testing is not required for post menopausal or surgically sterilized women.
I can take care of myself and perform daily activities.
Creatinine less than or equal to 1.6 mg/dL (at time of study entry).
See 8 more

Exclusion Criteria

I haven't had chemotherapy or radiation in the last 3 weeks, except for ibrutinib or venetoclax.
I have not taken inotuzumab ozogamicin in the last 3 weeks.
I am HIV positive.
See 7 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Treatment

Patients receive inotuzumab ozogamicin and chemotherapy before stem cell transplantation

2 weeks
Multiple visits for IV administration

Stem Cell Transplantation

Patients undergo stem cell transplantation and receive supportive care

1 week
Inpatient stay for transplantation

Post-Transplant Treatment

Patients receive inotuzumab ozogamicin and supportive care post-transplant

6 months
Regular visits for IV administration and monitoring

Maintenance

Patients receive maintenance therapy with inotuzumab ozogamicin

Up to 100 days post-transplant
Periodic visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years
Periodic follow-up visits

Treatment Details

Interventions

  • Bendamustine
  • Inotuzumab Ozogamicin
  • Melphalan
Trial OverviewThe trial tests the safety and effectiveness of inotuzumab ozogamicin combined with fludarabine and other chemotherapies before and after stem cell transplantation to treat leukemia or lymphoma. It aims to see if this combination can control cancer better than current methods while managing potential complications like graft-versus-host disease using tacrolimus and filgrastim.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Group II (inotuzumab ozogamicin, chemotherapy, transplant)Experimental Treatment8 Interventions
Recipients of haploidentical or mismatched unrelated stem cell transplant: Patients will receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on day -3 to -2, total body irradiation on day -1, and tacrolimus IV continuously beginning on day -2 then orally (PO) once daily (QD) or twice daily (BID) for about 6 months. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients receive cylophosphamide IV over 3 hours and mesna IV on days +3 to +4 and filgrastim-sndz subcutaneously (SC) QD beginning 1 week after the transplant until blood cell levels return to normal.
Group II: Group I (inotuzumab ozogamicin, chemotherapy, transplant)Experimental Treatment8 Interventions
Recipients of haploidentical or mismatched unrelated stem cell transplant: Patients will receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, fludarabine IV over 1 hour on days -5 to -2, melphalan IV over 30 minutes on day -3 to -2, total body irradiation on day -1, and tacrolimus IV continuously beginning on day -2 then orally (PO) once daily (QD) or twice daily (BID) for about 6 months. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients receive cylophosphamide IV over 3 hours and mesna IV on days +3 to +4 and filgrastim-sndz subcutaneously (SC) QD beginning 1 week after the transplant until blood cell levels return to normal.

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

🇺🇸
Approved in United States as Treanda for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
🇪🇺
Approved in European Union as Ribomustin for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
  • Multiple myeloma
🇨🇦
Approved in Canada as Levact for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma
🇯🇵
Approved in Japan as Bendamustine hydrochloride for:
  • Chronic lymphocytic leukemia
  • Non-Hodgkin lymphoma

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+

Findings from Research

Bendamustine has shown significant efficacy as a first-line treatment for chronic lymphocytic leukaemia (CLL), improving progression-free survival and overall response rates compared to chlorambucil in a phase III study with a median follow-up of 35 months.
In patients with rituximab-refractory indolent non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM), bendamustine monotherapy and combination therapy with prednisone demonstrated high response rates and prolonged time to treatment failure, indicating its effectiveness in these conditions.
Bendamustine: a review of its use in the management of chronic lymphocytic leukaemia, rituximab-refractory indolent non-Hodgkin's lymphoma and multiple myeloma.Hoy, SM.[2021]
Bendamustine demonstrated a high objective response rate of 74.3% in 99 patients with relapsed/refractory Hodgkin and non-Hodgkin lymphoma, indicating its efficacy as a salvage treatment after multiple lines of chemotherapy.
The most common side effects included lymphopenia, anemia, and neutropenia, with serious side effects occurring in a minority of patients, suggesting that while bendamustine is effective, monitoring for these side effects is important.
Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study.Karadurmus, N., Paydas, S., Esin, E., et al.[2022]
In a study involving 20 pediatric patients with low- and intermediate-risk Hodgkin lymphoma, a single-day dose of 180 mg/m2 of bendamustine was found to be safe and well tolerated, with no significant toxicities causing treatment delays.
Age was a factor influencing the clearance of bendamustine, accounting for 23% of variability among individuals, but this did not impact the overall safety and tolerability of the treatment.
Pharmacokinetics and safety of bendamustine in the BEABOVP regimen for the treatment of pediatric patients with Hodgkin lymphoma.Purvis, KN., Swanson, HD., Niloy, KK., et al.[2023]

References

Bendamustine: a review of its use in the management of chronic lymphocytic leukaemia, rituximab-refractory indolent non-Hodgkin's lymphoma and multiple myeloma. [2021]
Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]
Pharmacokinetics and safety of bendamustine in the BEABOVP regimen for the treatment of pediatric patients with Hodgkin lymphoma. [2023]
Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. [2015]
Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. [2015]
Long-term safety experience with bendamustine for injection in a real-world setting. [2017]
Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. [2015]
Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. [2022]
Bendamustine in the treatment of chronic lymphocytic leukemia. [2015]