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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for people with leukemia or lymphoma, focusing on a drug called inotuzumab ozogamicin. The main goal is to determine if this drug, combined with chemotherapy and a stem cell transplant, is safe and effective in controlling the disease. Inotuzumab ozogamicin targets specific cancer cells to deliver a powerful chemotherapy drug directly to them. This trial may suit individuals with CD22-positive leukemia or lymphoma who have not succeeded with other treatments. Participants must be eligible for a stem cell transplant and meet specific cancer types or conditions outlined in the trial criteria. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inotuzumab ozogamicin, a drug for certain types of leukemia, presents some known safety concerns. The most serious issues include infections and a liver problem called VOD. Other common side effects are fever, bleeding, and a decrease in white blood cells that help fight infections.

Melphalan, another chemotherapy drug, also carries risks. It can cause allergic reactions, including severe ones like anaphylaxis, a dangerous allergic reaction. It may also lead to fever and low white blood cell counts, similar to inotuzumab ozogamicin. Additionally, there is a risk of developing other cancers later on.

Both treatments have been studied extensively and are generally well-understood in terms of safety. However, anyone considering joining a trial should discuss these potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about inotuzumab ozogamicin combined with chemotherapy for leukemia and lymphoma because it offers a novel approach to treating these cancers. Unlike traditional chemotherapy that broadly targets rapidly dividing cells, inotuzumab ozogamicin is an antibody-drug conjugate that specifically targets CD22, a protein found on the surface of cancerous B-cells. This targeted action allows for more direct delivery of the drug to the cancer cells, potentially reducing side effects and improving effectiveness. Additionally, this treatment is paired with a stem cell transplant, which can help restore healthy blood cells more efficiently. This combination holds promise for improved outcomes compared to standard chemotherapy treatments.

What evidence suggests that this trial's treatments could be effective for leukemia or lymphoma?

Research has shown that inotuzumab ozogamicin effectively treats certain types of leukemia and lymphoma, with about 74% of patients experiencing complete or partial remission. In this trial, participants will receive inotuzumab ozogamicin alongside chemotherapy and a stem cell transplant. Bendamustine, when combined with another chemotherapy drug called fludarabine, has an overall response rate of 77%. High doses of melphalan have led to a complete response in 66.2% of blood cancer cases. These treatments work together to target and destroy cancer cells, leading to better outcomes for patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Issa F. Khouri

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

Serum glutamate pyruvate transaminase (SGPT) < 2 x upper limit of normal (ULN) (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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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, 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 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 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 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]

Citations

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Bendamustine: Safety and Efficacy in the Management of ... Efficacy of bendamustine was comparable in different indolent histological subtypes; ORR was 74% among the 62 patients who had FL and 71% among the 21 patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2697069/

Bendamustine (Treanda) For Chronic Lymphocytic Leukemia An overall response rate of 77% (17/22) has also been noted with bendamustine plus fludarabine (Fludara, Bayer/Ben Venue) combination therapy. ADVERSE EVENTS.

3. ashpublications.org ashpublications.org/bloodadvances/article/8/4/878/498748/Safety-of-bendamustine-for-the-treatment-of

Safety of bendamustine for the treatment of indolent non ... Long-term safety data for this trial reported a fatal AE event rate of ∼6% for bendamustine-treated patients at a median follow-up of 7.9 years.

4. theoncologynurse.com theoncologynurse.com/articles/15613-first-article-efficacy-of-bendamustine-in-chronic-lymphocytic-leukemia-ton2

Efficacy of Bendamustine in Chronic Lymphocytic ... 10 Studies have shown significantly higher response rates, longer duration of remission, and longer progression-free survival (PFS) rates in patients treated ...

5. haematologica.org haematologica.org/article/view/8525

Efficacy of bendamustine and rituximab as first salvage ... Dose reduction of over 10% of the planned dose of bendamustine (i.e. <70 mg/m) was recorded in 28.9% of cases; a treatment delay occurred in ...

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BESPONSA® (inotuzumab ozogamicin) Safety Information BESPONSA has a BOXED WARNING for VOD and post-HSCT NRM · The most common (≥2%) serious adverse reactions (ARs) were infection, febrile neutropenia, hemorrhage, ...

7. besponsa.pfizerpro.com besponsa.pfizerpro.com/efficacy/adult-clinical-data%E2%80%94ino-vate

BESPONSA® (inotuzumab ozogamicin) CR/CRi | Safety Info Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.

8. besponsa.pfizerpro.com besponsa.pfizerpro.com/safety/pediatric-safety-data

BESPONSA® (inotuzumab ozogamicin) Safety Information The most common serious adverse reactions (ARs) to BESPONSA in >2% of patients included infection, febrile neutropenia, VOD, hemorrhage, pyrexia, and multiorgan ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12165494/

Safety evaluation of inotuzumab ozogamicin This study underscores the potential ADEs and associated risks with the clinical application of InO, with particular emphasis on the risks of VOD, infections, ...

10. ema.europa.eu ema.europa.eu/en/documents/product-information/besponsa-epar-product-information_en.pdf

Besponsa, INN-inotuzumab ozogamicin The safety and efficacy of BESPONSA in children aged 0 to < 18 years have not been established. Currently available data are described in sections 4.8, 5.1 and ...