Immunotherapy + Chemotherapy for Acute Lymphoblastic Leukemia

Overseen By Elias Jabbour, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Burkitt's leukemia, T-cell ALL, active heart disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 cycles, alternating every 3-4 weeks

276 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of new and existing treatments for people with acute lymphoblastic leukemia (ALL). It focuses on the effectiveness of inotuzumab ozogamicin, a targeted therapy, in combination with chemotherapy against this cancer. The trial seeks to determine the optimal dose and identify any side effects. Suitable participants have ALL and have not undergone extensive prior treatment, or have health conditions like heart or lung issues that make intensive chemotherapy unsuitable. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that inotuzumab ozogamicin has been safe in past studies. Patients with B-cell precursor acute lymphoblastic leukemia have generally tolerated it well. Many studies have found that patients responded positively to the treatment, and side effects were usually manageable.

Additionally, blinatumomab is an immunotherapy that aids the immune system in fighting cancer. It has been used in other treatments and is usually well-tolerated by patients. The chemotherapy drugs in the trial, such as cyclophosphamide and methotrexate, are standard and have known side effects, which are typically managed with medical guidance.

Although the trial is in its early stages, focusing on safety and dosage, current data suggests that the treatment is generally safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for acute lymphoblastic leukemia because they bring innovative approaches to tackling the disease. Inotuzumab ozogamicin, a key component in the treatment, is an antibody-drug conjugate that targets CD22 on leukemia cells, delivering a potent chemotherapy agent directly into the cancerous cells, which could potentially reduce harm to healthy cells. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells, leading to broad side effects. Additionally, combining inotuzumab ozogamicin with a range of chemotherapeutic agents and immunotherapies like blinatumomab offers a multi-pronged attack on the leukemia, which may improve effectiveness and outcomes for patients.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that inotuzumab ozogamicin effectively treats acute lymphoblastic leukemia (ALL), particularly in patients unresponsive to previous treatments. Studies have found that using inotuzumab ozogamicin alone results in high remission rates for relapsed or hard-to-treat ALL, with about 73% of patients responding after just one treatment cycle. This treatment targets cancer cells and delivers a toxic substance directly to them, killing the cells. In this trial, participants will receive inotuzumab ozogamicin combined with chemotherapy, which might enhance its effectiveness, as chemotherapy also stops cancer cells from growing and dividing. Overall, inotuzumab ozogamicin shows promise in improving outcomes for ALL patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 60+ with untreated acute lymphoblastic leukemia (ALL), including those unfit for intensive chemotherapy due to comorbidities like heart or kidney disease. It's also open to any age with refractory-relapsed ALL, certain high-grade B-cell lymphomas, and marrow involvement. Excluded are those with newly diagnosed Burkitt's Leukemia/Lymphoma, T-cell ALL/lymphoma, active heart disease, ejection fraction <40%, active hepatitis, or who are pregnant/breastfeeding.

Inclusion Criteria

Patients age 60 years and older unfit for intensive chemotherapy with one or more comorbidities (e.g., renal insufficiency, heart disease, cardio-vascular disease, uncontrolled hypertension, diabetes, respiratory problems, among others) and a PS of ≥ 1. All ages of Jehovah's witness are eligible. Zubrod performance status 0-3. Adequate liver function (bilirubin < 1.95 mg/dL and SGPT or SGOT < 3 x upper limit of normal [ULN], unless considered due to tumor), and renal function (estimated creatinine clearance ≥50 mL/min/1.73 m2). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is < 2.6 mg/dL and creatinine < 3 mg/dL. Provision of written informed consent. Patients in first remission are eligible. Patients with refractory-relapsed ALL, Burkitt lymphoma, Burkitt-like lymphoma with 11q aberration, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified with marrow involvement of any age are eligible

I am 60 or older with untreated ALL, and may have had minimal prior therapy.

I am 18-59 years old with untreated ALL, have certain health issues, and may or may not have started treatment.

Exclusion Criteria

I do not have severe heart disease.

I do not have active hepatitis.

Pregnant or breast-feeding women are excluded

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inotuzumab ozogamicin in combination with low-intensity chemotherapy, including cyclophosphamide, vincristine, dexamethasone, methotrexate, and cytarabine, across multiple cycles

Up to 10 cycles, alternating every 3-4 weeks

Maintenance Therapy

Participants receive mercaptopurine, methotrexate, vincristine, prednisone, and blinatumomab over a long-term period

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Cyclophosphamide
• Cytarabine
• Dexamethasone
• Inotuzumab Ozogamicin
• Mercaptopurine
• Methotrexate
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial tests the safety and effectiveness of inotuzumab ozogamicin combined with chemotherapy in treating ALL. Inotuzumab ozogamicin targets cancer cells by delivering a toxin directly to them. The study includes other drugs like blinatumomab that help the immune system fight cancer and various chemotherapies aimed at stopping cancer cell growth.

How Is the Trial Designed?

Group I: Arm III (inotuzumab ozogamicin, combination chemotherapy) Experimental Treatment 8 Interventions

See Detailed Description Arm III

Group II: Arm II (inotuzumab ozogamicin, combination chemotherapy) Experimental Treatment 11 Interventions

See Detailed Description Arm II

Group III: Arm I (inotuzumab ozogamicin, combination chemotherapy) Experimental Treatment 11 Interventions

See Detailed Description Arm I

Blinatumomab is already approved in European Union, United States for the following indications:

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

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

The FDA has approved three innovative therapies for relapsed/refractory B-cell acute lymphoblastic leukemia, including inotuzumab ozogamicin and blinatumomab, which have significantly changed treatment options for this disease.

Understanding the unique toxicities and adverse effects of these therapies is crucial for safe administration, and the article provides recommendations for preventing and managing these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. Conde-Royo, D., Juárez-Salcedo, LM., Dalia, S.[2020]

In a study of 34 adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), blinatumomab achieved a complete remission (CR) rate of 69%, with 78% of those patients reaching minimal residual disease (MRD) negativity, indicating effective treatment outcomes.

Inotuzumab ozogamicin showed an even higher CR rate of 94% in patients with overt r/r B-ALL, with 67% achieving MRD negativity, suggesting both treatments are highly effective salvage options for this aggressive leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab or Inotuzumab Ozogamicin as Bridge to Allogeneic Stem Cell Transplantation for Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis. Stelmach, P., Wethmar, K., Groth, C., et al.[2021]

In a study of 29 children with acute lymphoblastic leukaemia (ALL) treated with blinatumomab and/or inotuzumab, the complete remission rate was 47.6%, indicating these therapies can be effective alternatives to traditional chemotherapy, especially in heavily pretreated patients.

Both treatments showed promise in reducing minimal residual disease and delaying further chemotherapy, with manageable safety profiles, as only six patients experienced grade 3 reversible non-haematological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Fuster, JL., Molinos-Quintana, A., Fuentes, C., et al.[2021]

Blinatumomab was found to be an effective treatment for older patients (median age 75) with newly diagnosed Philadelphia chromosome-negative B-acute lymphoblastic leukemia (ALL), achieving a complete remission rate of 66%.

The 3-year disease-free survival and overall survival rates were both 37%, indicating promising outcomes for this patient population, particularly for those with poor-risk cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. Advani, AS., Moseley, A., O'Dwyer, KM., et al.[2023]

In a study of 48 patients with relapsed or refractory acute lymphoblastic leukemia (ALL), the combination of inotuzumab and low-intensity mini-HCVD chemotherapy resulted in a high response rate of 92%, with 73% achieving complete remission.

The treatment showed promising long-term outcomes, with a median overall survival of 25 months and a 2-year overall survival rate of 54%, indicating that this combination therapy may be more effective than traditional intensive chemotherapy options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoimmunotherapy with inotuzumab ozogamicin combined with mini-hyper-CVD, with or without blinatumomab, is highly effective in patients with Philadelphia chromosome-negative acute lymphoblastic leukemia in first salvage. Jabbour, E., Sasaki, K., Ravandi, F., et al.[2020]

In the phase 3 TOWER study, blinatumomab showed a significant overall survival benefit compared to standard-of-care chemotherapy in adults with relapsed or refractory Philadelphia chromosome-negative B-precursor acute lymphoblastic leukemia, involving 267 patients who received a median of 2 cycles of treatment.

After adjusting for treatment duration, blinatumomab had lower exposure-adjusted event rates for serious adverse events compared to standard chemotherapy, particularly for infections and cytopenias, indicating it is a well-tolerated treatment option despite a higher rate of cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-adjusted adverse events comparing blinatumomab with chemotherapy in advanced acute lymphoblastic leukemia. Stein, AS., Larson, RA., Schuh, AC., et al.[2020]

Blinatumomab has been approved for treating relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL), showing a significant improvement in overall survival and complete remission rates compared to standard chemotherapy, with a median survival of 7.7 months versus 4.0 months for chemotherapy.

In clinical trials, blinatumomab demonstrated a complete remission rate of 34% in Philadelphia chromosome (Ph)-negative ALL and 31% in Ph-positive ALL, while also presenting some adverse events like cytokine release syndrome and neurological issues, although it had fewer cases of neutropenia and infections compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B-Cell Acute Lymphoblastic Leukemia. Pulte, ED., Vallejo, J., Przepiorka, D., et al.[2019]

Blinatumomab is a promising new treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, showing effectiveness in targeting and destroying tumor cells by engaging both T-cells and B-cells.

While there are potential side effects like immunological toxicities and cytokine release syndrome, most patients tolerate blinatumomab well, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Lee, KJ., Chow, V., Weissman, A., et al.[2022]

Blinatumomab, a bispecific T-cell engager, shows significant efficacy in treating refractory or relapsed acute lymphoblastic leukemia (ALL), achieving complete response rates of 39% to 69% and a median overall survival of 7.7 months, compared to 4.0 months with traditional chemotherapy.

The treatment has a favorable safety profile, with manageable side effects such as cytokine-release syndrome and reversible neurological issues, making it a promising option for both adult and pediatric patients with R/R ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. Queudeville, M., Handgretinger, R., Ebinger, M.[2020]

In a study of 64 adults with relapsed/refractory acute lymphoblastic leukemia (ALL) after stem cell transplantation, blinatumomab achieved a complete remission (CR) or CR with partial hematologic recovery in 45% of patients within the first two treatment cycles, indicating its efficacy as a salvage therapy.

While blinatumomab showed promising results, it was associated with significant adverse events, including grade 3 and 4 complications in 31% and 44% of patients, respectively, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab for Acute Lymphoblastic Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Stein, AS., Kantarjian, H., Gökbuget, N., et al.[2020]

Blinatumomab significantly improves overall survival in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), with a median survival of 7.7 months compared to 4.0 months with traditional chemotherapy.

Patients treated with blinatumomab report a higher quality of life and lower financial burden compared to those receiving standard chemotherapy, making it a more cost-effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of blinatumomab on patient outcomes in relapsed/refractory acute lymphoblastic leukemia: evidence to date. Hathaway, L., Sen, JM., Keng, M.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427359/

Real‐World Data on Inotuzumab Ozogamicin for Adult ... InO demonstrated high remission and MRD negativity rates in Chilean patients with R/R ALL, with OS and PFS comparable to existing research.

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

BESPONSA® (inotuzumab ozogamicin) CR/CRi | Safety Info In the remission analysis population of 109 patients randomized to receive BESPONSA, 73% (n=64/88) responded in Cycle 1 and 24% (n=21/88) responded in Cycle 2.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1422/531484/Safety-and-Efficacy-Results-of-Dose-Adjusted

Safety and Efficacy Results of Dose-Adjusted Inotuzumab ... Conclusions: The results of this study indicate that dose-adjusted InO is a well-tolerated and effective treatment option for B-ALL adults with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12533514/

Inotuzumab ozogamicin in adult acute lymphoblastic leukemia Outcomes have been historically poor in adults with relapsed/refractory (R/R) B-cell ALL, with a 5-year overall survival (OS) rate of <10% with ...

5. haematologica.org haematologica.org/article/view/11921

Efficacy and safety of currently approved and lower starting ... This study evaluated efficacy and safety of the currently approved InO starting dose and a lower dose in adults with R/R ALL who were eligible for HSCT.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40120068/

INO-CD22: A multicenter, real-world study of inotuzumab ... Conclusions: Despite the limitations of retrospective studies, the INO-CD22 study highlights the favorable safety profile and clinical activity ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6541

Outcomes in patients with B-cell precursor acute ... In this pooled analysis of pts treated with InO for R/R B-ALL, efficacy and safety outcomes were broadly consistent across BMI groups.