Inotuzumab Ozogamicin + Chemotherapy for Leukemia or Lymphoma

Overseen By Issa F Khouri

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: HIV, Active infection, Hepatitis B/C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 3 7 8 9}

Research Team

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).

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.

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 Overview The 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

Group I: Group II (inotuzumab ozogamicin, chemotherapy, transplant) Experimental Treatment 8 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 Treatment 8 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

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Bendamustine is a unique cancer treatment that combines alkylating and antimetabolite properties, making it effective against certain blood cancers like chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

It has been approved by the US FDA for patients whose cancer has not responded to or has progressed after rituximab treatment, and it can be used alone or in combination with other therapies, showing promising efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ujjani, C., Cheson, BD.[2015]

Bendamustine, a mechlorethamine derivative, has shown significant efficacy in treating chronic lymphocytic leukemia (CLL) and rituximab-refractory indolent B-cell non-Hodgkin lymphoma (NHL), with clinical trials demonstrating a greater overall response rate and longer progression-free survival compared to chlorambucil.

The drug has good oral bioavailability but is primarily administered intravenously, and while it has some dose-limiting hematologic toxicity, non-hematologic side effects are generally mild, making it a viable treatment option for various hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Dennie, TW., Kolesar, JM.[2015]

Bendamustine hydrochloride has been associated with serious adverse events such as Stevens-Johnson syndrome and toxic epidermal necrolysis, leading to important label updates regarding its safety and administration.

Despite these risks, the long-term pharmacovigilance data suggest that bendamustine maintains a favorable risk-benefit profile, making it a valuable treatment option for patients with chronic lymphocytic leukemia and relapsed indolent B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety experience with bendamustine for injection in a real-world setting. Martin, P., Barr, PM., James, L., et al.[2017]

Bendamustine, when combined with rituximab, shows strong effectiveness in treating relapsed and refractory indolent lymphoma, with positive results observed in various patient groups, including those who have not previously received rituximab.

Interim results from a phase III trial indicate that the bendamustine and rituximab combination may be a promising alternative to the standard CHOP regimen for treating indolent lymphomas, suggesting a favorable safety and efficacy profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. Rummel, MJ.[2015]

In a study of 67 adults with relapsed indolent B-cell or mantle cell lymphoma, the combination of bendamustine and rituximab achieved a high overall response rate of 92%, with a median duration of response of 21 months.

The treatment was generally well tolerated, although myelosuppression was the primary side effect, affecting 36% of patients with grade 3 or 4 neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. Robinson, KS., Williams, ME., van der Jagt, RH., et al.[2022]

Bendamustine has demonstrated high efficacy in treating chronic lymphocytic leukemia (CLL), with overall response rates ranging from 56% to 93% in Phase I/II trials, and significantly higher response rates compared to chlorambucil in preliminary Phase III trials.

The main side effect of bendamustine is hematological toxicity, particularly leukopenia, which is a decrease in white blood cells that can increase the risk of infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in the treatment of chronic lymphocytic leukemia. Knauf, W.[2015]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Bendamustine: a review of its use in the management of chronic lymphocytic leukaemia, rituximab-refractory indolent non-Hodgkin's lymphoma and multiple myeloma. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of bendamustine in the BEABOVP regimen for the treatment of pediatric patients with Hodgkin lymphoma. [2023]

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

Bendamustine in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. [2015]

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

Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Long-term safety experience with bendamustine for injection in a real-world setting. [2017]

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

Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. [2015]

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

Phase II multicenter study of bendamustine plus rituximab in patients with relapsed indolent B-cell and mantle cell non-Hodgkin's lymphoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Bendamustine in the treatment of chronic lymphocytic leukemia. [2015]