Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Recurrence

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Disease Attributes

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Acute Graft Versus Host Disease

Micronutrients

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Hematinics

Vitamins

Leucovorin

Antibodies

Antibodies, Monoclonal

Dexamethasone

Cytarabine

Cyclophosphamide

Levoleucovorin

Methotrexate

Prednisone

Rituximab

Vincristine

Lenograstim

Dexamethasone acetate

BB 1101

Folic Acid

Immunoglobulins

Mercaptopurine

Cortisone

Ichthammol

Mesna

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

Antimetabolites

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Adjuvants, Immunologic

Antidotes

Protective Agents

Trace Elements

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

Filgrastim-sndz

Pegfilgrastim

Tagraxofusp-erzs

Nicholas Short, MD

Nicholas Short

This phase Ib/II trial studies the effects of tagraxofusp and low-intensity chemotherapy in treating patients with CD123 positive acute lymphoblastic leukemia or lymphoblastic lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Tagraxofusp consists of human interleukin 3 (IL3) linked to a toxic agent called DT388. IL3 attaches to IL3 receptor positive cancer cells in a targeted way and delivers DT388 to kill them. Chemotherapy drugs, 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 tagraxofusp with chemotherapy may help control CD123 positive relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma.

PRIMARY OBJECTIVE:

I. To evaluate the overall response rate (complete response \[CR\] + CR with inadequate count recovery \[CRi\]) of the regimen within 3 cycles.

SECONDARY OBJECTIVES:

I. Evaluate other clinical efficacy endpoints (CR rate, minimal residual disease \[MRD\] negativity, duration of response \[DOR\], relapse-free survival \[RFS\] overall survival \[OS\]).

II. Determine the proportion of patients proceeding to allogeneic stem cell transplantation (allo-SCT).

III. Determine the safety of the combination regimen.

EXPLORATORY OBJECTIVES:

I. To determine CD123 expression levels pre- and post-therapy. II. To correlate baseline CD123 expression with response rates and duration of response.

III. To evaluate change in apoptotic protein expression and alterations in cellular signaling pathways using cytometry by time of flight (CyTOF).

IV. To determine baseline gene expression profile in order to identify ALL subtypes and correlate with clinical outcomes and response to single-agent tagraxofusp-erzs (tagraxofusp).

OUTLINE:

TAGRAXOFUSP AND CHEMOTHERAPY PHASE:

CYCLE 1: Patients receive tagraxofusp-erzs intravenously (IV) over 15 minutes on days 1-5.

CYCLES 2 AND 4: Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3, cyclophosphamide IV over 3 hours twice daily (BID) and mesna IV on days 4-6, vincristine IV over 15 minutes on days 4 and 15, dexamethasone IV over 30 minutes or orally (PO) on day 4-7 and 14-17, methotrexate intrathecally (IT) on day 5, and filgrastim-sndz subcutaneously (SC) or pegfilgrastim SC on day 8, and cytarabine IT on day 10. Patients may receive rituximab IV over 4-6 hours on days 4 and 14.

CYCLES 3 AND 5: Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-3, methotrexate IV over 24 hours on day 4, cytarabine IV over 3 hours BID on days 5-6, filgrastim-sndz SC or pegfilgrastim SC on day 6, methotrexate IT and cytarabine IT on day 11. Patients may receive rituximab IV over 4-6 hours on days 4 and 11. Beginning about 12 hours after the day 4 dose of methotrexate, patients may also receive leucovorin IV over 15 minutes, 4 times a day for about 8 doses.

CYCLES 6 AND 8: Patients receive cyclophosphamide IV over 3 hours BID and mesna IV on days 1-3, vincristine IV over 15 minutes on days 1 and 11, dexamethasone IV over 30 minutes or PO on day 1-4 and 11-14, and filgrastim-sndz SC or pegfilgrastim SC on day 5.

CYCLES 7 AND 9: Patients receive methotrexate IV over 24 hours on day 1, cytarabine IV over 3 hours BID on days 2-3, and filgrastim-sndz SC or pegfilgrastim SC on day 4. Beginning about 12 hours after the day 1 dose of methotrexate, patients may receive leucovorin IV over 15 minutes, 4 times a day for about 8 doses.

Cycle 1 is 21 days. Treatment repeats every 28 days for cycles 2-9 in the absence of disease progression or unacceptable toxicity.

TAGRAXOFUSP AND MAINTENANCE PHASE:

CYCLES 1-3, 5-7, 9-11, 13-15: Patients receive mercaptopurine PO three time daily (TID) on days 1-28, prednisone PO once daily (QD) on day 1-5, methotrexate PO once every week (QW) and vincristine IV over 15 minutes every 4 weeks.

CYCLES 4, 8, and 12: Patients receive tagraxofusp-erzs IV over 15 minutes on days 1-5.

Treatment repeats every 28 days for 15 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Tagraxofusp and Low-Intensity Chemotherapy for the Treatment of CD123 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Phase Ib/II Study of the Combination of Low-Intensity Chemotherapy and Tagraxofusp in Patients With Acute Lymphoblastic Leukemia (ALL)

Will be monitored simultaneously using the Bayesian approach. Will be estimated along with 95% credible intervals. Chi-square tests or Fisher's exact test will be used to evaluate the association between patient's prognostic factor and response.

Will be estimated along with 95% credible intervals. Chi-square tests or Fisher's exact test will be used to evaluate the association between patient's prognostic factor and response.

Kaplan-Meier method will be used to estimate the RFS.

Kaplan-Meier method will be used to estimate the overall survival.

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Mastocytosis

Leukemia, Myeloid

Hematologic Neoplasms

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Leukemia, Hairy Cell

Mastocytosis, Systemic

Acute Disease

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Hairy Cell Leukemia

Systemic Mastocytosis

Dendritic Cell Tumor

Blastic Plasmacytoid Dendritic Cell

Chronic Myeloproliferative Disorders

Antipyretics

Analgesics

Anti-Allergic Agents

Central Nervous System Depressants

Acetaminophen

Ibuprofen

Antibodies, Bispecific

Diphenhydramine

Promethazine

Ranitidine

Ranitidine bismuth citrate

Analgesics, Non-Narcotic

Anti-Inflammatory Agents, Non-Steroidal

Cyclooxygenase Inhibitors

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Antacids

Anti-Ulcer Agents

Histamine H2 Antagonists

INDUCTION THERAPY: Patients receive flotetuzumab via continuous IV infusion on days 1-28. Patients who achieve SD/PR (Cohort A) or PR/CI (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/MMR (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

Flotetuzumab

Ibrahim T Aldoss

This phase I trial studies the best dose and side effects of flotetuzumab for the treatment of patients with blood cancers (hematological malignancies) that have spread to other places in the body (advanced) and have come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Flotetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (recommended phase 2 dose, RP2D) of flotetuzumab, when given as a single agent.

II. Evaluate the safety and tolerability of flotetuzumab in CD123-positive advanced acute lymphoblastic leukemia (ALL) (Cohort A) and other hematological malignancies (Cohort B), by evaluation of toxicities including: type, frequency, severity, attribution, and duration of the toxicity.

SECONDARY OBJECTIVES:

I. Obtain preliminary estimates of remission; (complete remission \[CR\], complete remission with incomplete count recovery \[CRi\], complete remission with partial hematological recovery \[CRh\] or morphologic leukemia free state \[MLFS\] in Cohort A or CR/molecular response \[MR\] in Cohort B) rate and duration.

II. Estimate 1-year overall survival. III. Evaluate minimal residual disease (MRD) status in responders in the ALL cohort.

IV. Evaluate the percentage of patients who receive subsequent allogeneic transplantation.

EXPLORATORY OBJECTIVES:

I. Examine immune profile pre- and post-treatment with flotetuzumab. II. Assess the association between CD123 expression and tumor response. III. Assess the association between alterations in tumor genetic or microenvironment with response.

IV. Assess cytokine levels during therapy.

OUTLINE: This is a dose-escalation study.

INDUCTION THERAPY: Patients receive flotetuzumab via continuous intravenous (IV) infusion on days 1-28. Patients who achieve stable disease (SD)/partial remission (PR) (Cohort A) or PR/clinical improvement (CI) (Cohort B), receive an additional induction cycle. Patients who achieve PR (Cohort A) or PR/CI/major molecular response (MMR) (Cohort B) after cycle 2 re-induction, may continue induction therapy for up to 4 more cycles.

CONSOLIDATION THERAPY: Patients who achieve CR/CRi/CRh/MLFS (Cohort A) or CR/MR (Cohort B) after cycle 1 or cycle 2 of induction therapy, receive flotetuzumab via continuous IV infusion on days 1-28 for up to 5 and 6 cycles, respectively, in the absence of disease progression or unacceptable toxicity. Patients with PR (Cohort A) or PR/CI/MMR (Cohort B) who have received up to 6 cycles of induction therapy may receive up to 2 cycles of consolidation therapy in the absence of disease progression or unacceptable toxicity.

SUPPORTIVE CARE: Patients also receive acetaminophen orally (PO) or ibuprofen PO every 8 hours for 48 hours, diphenhydramine or equivalent IV or PO every 8 hours for 48 hours, ranitidine or equivalent IV every 8 hours for 48 hours, and dexamethasone IV up to 30 minutes prior to dosing and then at 12 hours after dosing on week 1 days 1 and 7.

After completion of study treatment, patients are followed up at 30 days, then every 3 months for 1 year.

Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies

A Phase 1 Trial to Evaluate the Safety of Single Agent Flotetuzumab in Advanced CD123-Positive Hematological Malignancies

Toxicity will be graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events version 5.0 except infusion-related reaction (IRR)/cytokine release syndrome (CRS) which will be by the modified criteria proposed by Lee et al. Safety and toxicity will be assessed for each cohort independently. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, probable association with the study treatment and reversibility or outcome.

Rates and 95% Clopper Pearson binomial confidence interval (CI) will be calculated for complete remission/response rate (confirmed complete remission \[CR\]/ complete remission with incomplete count recovery \[CRi\]/ complete remission with partial hematological recovery \[CRh\] \[Cohort A\] or CR/molecular response \[MR\] \[Cohort B\]). Remission rates will also be explored based on number/type of prior therapy(ies), the presence of extramedullary disease at the time of starting therapy, disease burden, and CD123 expression intensity.

Assessed by multi-color flow cytometry in ALL the cohorts.

Will be estimated using the product-limit method of Kaplan and Meier.

Number/percent of patients who proceed to hematopoietic cell transplantation after achieving complete response/ complete remission

National Cancer Institute (NCI)

City of Hope Medical Center

Leukemia, Myeloid, Acute

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Leukemia of Ambiguous Lineage

Neuroprotective Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Fludarabine

Fludarabine phosphate

Daunorubicin

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Hydrocortisone-17-butyrate

Anti-Bacterial Agents

Antibiotics, Antitubercular

Patients receive IMGN632 IV on days 1 and 22. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

CYCLE 1: Patients receive IMGN632 IV on days 1 and 22 and CPX-351 IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients with CNS1 also receive ITT consisting of methotrexate IT, hydrocortisone or prednisolone IT, and cytarabine IT on day 0 of cycle 1 (NOTE: Patients who received IT cytarabine or ITT at time of diagnostic LP do not need to repeat ITT on day 0 if given within 7 days of starting protocol therapy). Patients with CNS2 receive ITT QW until the CSF is clear for a maximum of 6 ITT treatments in the absence of disease progression or unacceptable toxicity.

CYCLE 2: Patients receive ITT on day 0, IMGN632 IV on days 1 and 22, fludarabine IV over 30 minutes QD on days 1-5, and cytarabine IV over 1-3 hours QD on days 1-5 in the absence of disease progression or unacceptable toxicity.

Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 of cycle 1 in the absence of disease progression or unacceptable toxicity. Patients then receive fludarabine IV over 30 minutes QD on days 1-5 of cycle 2 and cytarabine IV over 1-3 hours QD on days 1-5 of cycle 2 in the absence of disease progression or unacceptable toxicity.

Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 of cycle 1 and IMGN632 IV on days 1 and 22 of cycle 1 in the absence of disease progression or unacceptable toxicity. Patients then receive fludarabine IV over 30 minutes QD on days 1-5 of cycle 2, cytarabine IV over 1-3 hours QD on days 1-5 of cycle 2, and IMGN632 IV on days 1 and 22 of cycle 2 in the absence of disease progression or unacceptable toxicity.

Anti-CD123 ADC IMGN632

Bone Marrow Aspiration and Biopsy

Fludarabine Phosphate

Hydrocortisone Sodium Succinate

Liposome-encapsulated Daunorubicin-Cytarabine

Matthew A Kutny

This phase I/II trial finds the highest safe dose of IMGN632 that can be given with other chemotherapy without causing severe side effects, studies what kind of side effects IMGN632 may cause, and determines whether IMGN632 is a beneficial treatment for leukemia in children that has come back after treatment or is difficult to treat. IMGN632 is a monoclonal antibody linked to a chemotherapy drug. IMGN632 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD123 receptors, and delivers the chemotherapy drug to kill them. Giving IMGN632 with other chemotherapy may cause the leukemia to stop growing or to shrink for a period of time.

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of anti-CD123 ADC IMGN632 (IMGN632) monotherapy in pediatric patients with second or greater relapse of CD123 positive leukemia or CD123 positive leukemia refractory to relapse therapy. (Cohort 1 \[Monotherapy Phase 1\]) II. To assess the flow-based overall response rate (complete remission \[CR\]/CR with incomplete blood count recovery \[CRi\]/CR with partial recovery of platelet count \[CRp\]) in patients with acute myeloid leukemia (AML) treated with IMGN632. (Cohort 1 \[Monotherapy Phase 1\]) III. To determine the safety, feasibility, and RP2D of IMGN632 in combination with liposome-encapsulated daunorubicin-cytarabine (DAUNOrubicin and cytarabine liposome) in pediatric patients with first relapse of CD123 positive AML. (Cohort 2 \[Combination Therapy Dose Finding\]) IV. To compare the minimal residual disease (MRD) negative flow-based overall response rate (CR/CRi/CRp) in pediatric patients with first relapse of CD123 positive AML randomized to two cycles of therapy including DAUNOrubicin and cytarabine liposome followed by fludarabine phosphate (fludarabine)/cytarabine with or without IMGN632. (Cohort 3 \[Randomized Phase 2\])

SECONDARY OBJECTIVE:

I. To characterize the pharmacokinetics of IMGN632 in a pediatric population. (Cohort 1 \[Monotherapy Phase 1\])

EXPLORATORY OBJECTIVES:

I. To describe the anti-leukemic activity (morphologic and flow-based CR/CRp/CRi after up to two cycles, rates of MRD negative response after up to 2 cycles, event free survival \[EFS\] and overall survival \[OS\]) of IMGN632 in patients with multiply relapsed or refractory relapsed pediatric leukemia including AML, B-cell acute lymphoblastic leukemia \[ALL\], T-cell ALL and mixed phenotype acute leukemia (MPAL). (Cohort 1) II. To describe the EFS, OS, cumulative incidence of relapse, and rate of subsequent stem cell transplant for patients with first relapse of AML randomized to treatment with up to two cycles of chemotherapy with or without IMGN632. (Cohort 3) III. To determine if CD123 expression on leukemic blasts (assessed by flow cytometry) correlates with clinical response to IMGN632. (All Cohorts) IV. To determine the cumulative incidence of left ventricular systolic dysfunction (LVSD), defined as an absolute decline in EF by \>= 10% to an ejection fraction (EF) value of \< 50%, or an absolute decline in shortening fraction (SF) by \>= 4% to an SF value of \< 25%, within 1 year of initiation of DAUNOrubicin and cytarabine liposome based therapy for relapsed pediatric AML.

V. To describe safety (adverse events) in pediatric leukemia patients treated with IMGN632 including long-term safety events related to treatment for up to 5 years. (All Cohorts)

OUTLINE: This is a phase I, dose-escalation study of IMGN632 followed by a phase II study. In phase I, patients with second or greater relapse or refractory relapsed disease of AML, B-ALL, T-ALL or MPAL with CD123 expression are assigned to Cohort I, while patients with CD123 positive AML in first relapse are assigned to Cohort II. In phase II, patients with first relapse of CD123 positive AML are assigned to Cohort III.

COHORT 1: Patients receive IMGN632 intravenously (IV) on days 1 and 22. Treatment repeats every 42 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

COHORT 2:

CYCLE 1: Patients receive IMGN632 IV on days 1 and 22 and liposome-encapsulated daunorubicin-cytarabine (CPX-351) IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. Patients with CNS1 also receive intrathecal triple therapy (ITT) consisting of methotrexate intrathecally (IT), hydrocortisone or prednisolone IT, and cytarabine IT on day 0 of cycle 1 (NOTE: Patients who received IT cytarabine or ITT at time of diagnostic lumbar puncture \[LP\] do not need to repeat ITT on day 0 if given within 7 days of starting protocol therapy). Patients with CNS2 receive ITT once weekly (QW) until the cerebrospinal fluid (CSF) is clear for a maximum of 6 ITT treatments in the absence of disease progression or unacceptable toxicity.

CYCLE 2: Patients receive ITT on day 0, IMGN632 IV on days 1 and 22, fludarabine IV over 30 minutes once daily (QD) on days 1-5, and cytarabine IV over 1-3 hours QD on days 1-5 in the absence of disease progression or unacceptable toxicity.

COHORT 3: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 of cycle 1 in the absence of disease progression or unacceptable toxicity. Patients then receive fludarabine IV over 30 minutes QD on days 1-5 of cycle 2 and cytarabine IV over 1-3 hours QD on days 1-5 of cycle 2 in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive CPX-351 IV over 90 minutes on days 1, 3, and 5 of cycle 1 and IMGN632 IV on days 1 and 22 of cycle 1 in the absence of disease progression or unacceptable toxicity. Patients then receive fludarabine IV over 30 minutes QD on days 1-5 of cycle 2, cytarabine IV over 1-3 hours QD on days 1-5 of cycle 2, and IMGN632 IV on days 1 and 22 of cycle 2 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for the first year, twice a year for year two and yearly visits until five years from enrollment.

Phase I non-randomized study followed by a phase II randomized study

A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat

A PedAL/EuPAL Phase 1/2 Trial of IMGN632 in Pediatric Patients With Relapsed or Refractory Leukemia

Patients enrolled onto the monotherapy Phase 1 arm will be grouped by disease type (acute myeloid leukemia \[AML\], B-cell acute lymphoblastic leukemia \[ALL\], early thymic precursor \[ETP\] T-cell ALL and mixed phenotype acute leukemia \[MPAL\]) and the anti-leukemic activity of IMGN632 monotherapy will be described.

Patients enrolled onto the monotherapy Phase 1 arm will be grouped by disease type (AML, B-cell ALL, ETP T-cell ALL and MPAL) and the anti-leukemic activity of IMGN632 monotherapy will be described.

Will be collected and the rate of subsequent stem cell transplant will be described by treatment arm. This will include data regarding the conditioning regimen used, stem cell donor source and transplant related toxicities such as veno-occlusive disease.

Will be summarized by treatment arm for patients with first relapse of AML treated during the randomized Phase 2.

CD123 expression on leukemic blasts will be analyzed at Hematologics, Inc. (Seattle, Washington \[WA\]) by multi-dimensional flow cytometry (MDF) utilizing a "difference from normal" flow cytometric technique. CD123 mean fluorescent intensity (MFI) will be quantified and converted to molecules per cell (MPC) using CD4 MFI on T cells as a reference. CD123 MPC will be assessed on bone marrow (or peripheral blood samples if bone marrow not available) at initial diagnosis and after cycle 1 of treatment for patients with first relapse of AML treated on the randomized phase 2 portion of this study. Outcomes, including OS, EFS, and MRD negative CR after cycle 1, will be correlated with CD123 MPC and compared between the groups of patients who did and did not receive the investigational therapy IMGN632 using Cox and logistic regression models.

Will be estimated with subsequent relapse and death considered competing events. Cox regression will be used to estimate adjusted hazard ratio (HR) comparing EFS and OS in patients with LVSD relative to patients with no LVSD. LVSD will be treated as a time-varying exposure introduced on the first occurrence during/ following salvage therapy. HRs will be determined separately for infection-associated or not infection-associated events. Exploratory analyses will be performed to assess the differential impact of infection vs. non-infection associated LVSD on survival.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tagraxofusp and Low-Intensity Chemotherapy for the Treatment of CD123 Positive Relapsed or Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma	NCT05032183	Recurrent Adult... Recurrent B Acu... Recurrent T Acu... Refractory B Ac... Refractory Lymp... Refractory T Ac...	Cyclophosphamid... Cytarabine Dexamethasone Filgrastim-sndz Leucovorin Mercaptopurine Mesna Methotrexate Pegfilgrastim Prednisone Rituximab Tagraxofusp-erz... Vincristine	18 Years - 70 Years	M.D. Anderson Cancer Center
Flotetuzumab for the Treatment of Relapsed or Refractory Advanced CD123-Positive Hematological Malignancies	NCT04681105	Recurrent Acute... Recurrent B Acu... Recurrent Blast... Recurrent Chron... Recurrent Hairy... Recurrent Hemat... Recurrent Hodgk... Recurrent T Acu... Refractory Acut... Refractory B Ac... Refractory Blas... Refractory Chro... Refractory Hair... Refractory Hema... Refractory Hodg... Refractory T Ac... Systemic Mastoc...	Acetaminophen Dexamethasone Diphenhydramine Flotetuzumab Ibuprofen Ranitidine	12 Years -	City of Hope Medical Center
A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat	NCT05320380	Recurrent Acute... Recurrent B Acu... Recurrent Mixed... Recurrent T Acu... Refractory Acut... Refractory B Ac... Refractory Mixe... Refractory T Ac...	Anti-CD123 ADC ... Bone Marrow Asp... Cytarabine Fludarabine Pho... Hydrocortisone ... Liposome-encaps... Methotrexate Prednisolone	12 Months - 22 Years	Children's Oncology Group
A Study of the Drug IMGN632 in Children With Leukemia That Has Come Back After Treatment or is Difficult to Treat	NCT05320380	Recurrent Acute... Recurrent B Acu... Recurrent Mixed... Recurrent T Acu... Refractory Acut... Refractory B Ac... Refractory Mixe... Refractory T Ac...	Anti-CD123 ADC ... Bone Marrow Asp... Cytarabine Fludarabine Pho... Hydrocortisone ... Liposome-encaps... Methotrexate Prednisolone	12 Months - 22 Years	Children's Oncology Group

Spots Global Cancer Trial Database for recurrent t acute lymphoblastic leukemia