Acute Leukemias of Ambiguous Lineage, B-cell Adult Acute Lymphoblastic Leukemia, Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia, Recurrent Adult Burkitt Lymphoma
Conditions
Brief summary
This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given together with combination chemotherapy in treating patients with relapsed or refractory acute leukemia. Immunotoxins, such as inotuzumab ozogamicin, can find cancer cells that express cluster of differentiation (CD)22 and kill them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving inotuzumab ozogamicin together with combination chemotherapy may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVES: I. To assess the safety of inotuzumab ozogamicin in combination with cyclophosphamide, vincristine (vincristine sulfate) and prednisone (CVP) and to determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's). SECONDARY OBJECTIVES: I. To estimate the preliminary activity (response rate: complete remission \[CR\] + complete remission with incomplete count recovery \[CRi\]) of this combination in the expansion cohort. II. To estimate the frequency and severity of toxicities of this combination in this patient population. OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin. Patients receive cyclophosphamide intravenously (IV) on day 1, vincristine sulfate IV on day 1, prednisone orally (PO) on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 1 year.
Interventions
DRUGcyclophosphamide
Given IV
DRUGvincristine sulfate
Given IV
DRUGprednisone
Given PO
BIOLOGICALinotuzumab ozogamicin
Given IV
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt's leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded * Patients must have evidence of acute leukemia in their peripheral blood or bone marrow; patients must have \>= 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration; at least \>= 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology * Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine * For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria: * Patient is in second salvage or more; OR * Patient was treated on the standard of care arm of B1931022 and failed therapy * Patients may have received prior allogeneic transplant or autologous transplant; however, patients with prior allogeneic bone marrow transplant will be eligible only if both of the following conditions are met: * The transplant must have been performed \>= 90 days prior to registration * The patient must not have \>= grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD within 14 days prior to registration * Patients known to have Philadelphia chromosome positive (Ph+) ALL must have either failed treatment or been intolerant to treatment with at least two second or third generation tyrosine kinase inhibitors * Patients must not have received prior treatment with inotuzumab ozogamicin; previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration * Patients must have Zubrod performance status 0-2 * Patients must not have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration with the following exceptions: * Monoclonal antibodies must not have been received for 1 week prior to registration * Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration. * Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any time frame prior to registration. FDA-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1). * All drug-related toxicities must have resolved to =\< grade 2 * Patients must not have a systemic bacterial, fungal, or viral infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment) * Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy * Patients must not have active central nervous system (CNS) involvement (by clinical evaluation); patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration; note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not required * Patients must have a peripheral blast count \< 25,000/uL within 2 days prior to registration; (treatment with hydroxyurea and steroids is permitted to bring the countdown) * Patients must have serum creatinine =\< 2 x institutional upper limits of normal (IULN) within 7 days prior to registration * Patients must have bilirubin =\< 2 x IULN within 7 days prior to registration (unless the bilirubin is primarily unconjugated) * Patients must have \< grade 2 neuropathy (sensory/motor) within 7 days prior to registration * Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x IULN within 7 days prior to registration * Patients with a history of a serious allergic or anaphylactic reaction to humanized monoclonal antibodies are not eligible * Patients must not have a history of chronic or active hepatitis B or C infection; patients must have negative hepatitis B and C serologies performed within 28 days prior to registration * Patients must not have evidence or history of veno-occlusive disease or sinusoidal obstruction syndrome * Patients must not have a cardiac ejection fraction \< 45% or the presence of New York Heart Association stage III or IV heart failure within 14 days prior to registration; either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) may be used to determine ejection fraction * Patients must not have a myocardial infarction within 6 months prior to registration * Patients must not have a history of clinically significant arrhythmia, prolonged corrected QT (QTc) interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registration * Patients must not have a screening corrected QT using Fridericia's formula (QTcF) interval \> 500 milliseconds (by Fridericia calculation) based on the average of triplicate electrocardiogram (EKG) performed within 7 days prior to registration; note that triplicate EKG is required at other timepoints * Patients must not have a history of chronic liver disease (or cirrhosis) * Patients who are known to be human immunodeficiency virus (HIV)+ are eligible providing they meet all of the following additional criteria within 28 days prior to registration: * CD4+ cells \>= 350/mm\^3 (nadir) * Viral load of \< 50 copies HIV messenger ribonucleic acid (mRNA)/mm\^3 if on combination antiretroviral therapy (cART) or \< 25,000 copies HIV mRNA if not on cART * No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet all of these criteria are not eligible for this study * Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration * Patients must have complete history and physical examination within 28 days prior to registration * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of reproductive potential if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, effective contraception also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * Prior malignancy other than acute leukemia is allowed, provided it is in remission and there is no plan to treat the malignancy at the time of registration * Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 14 days prior to registration to S1312; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other time points * Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * Patients planning to enroll in this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia | 28 days | To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is \< 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and Severity of Toxicities | Up to 3 years | Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event. |
| Response Rate (CR+CRi) Among Expansion Cohort | Up to 3 years | The response rate (CR + CRi) is defined as the rate of complete remission (CR) + complete remission with incomplete count recovery (CRi). Complete remission (CR) is defined as \< 5% marrow aspirate blasts, neutrophils ≥ 1000/uL, platelets \> 100,000/uL, no blasts in peripheral blood, and C1 Extramedullary disease status. C1 Extramedullary disease status is characterized by complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions for which the following must be true: for participants with at least one measurable lesion, all lesions must have reduced by 75% in sum of products of greatest diameters (SPD), have no new lesions, and the spleen and other previously enlarged organs must have regressed in size. Complete remission with incomplete platelet recovery (CRi) is defined the same as CR, except absolute neutrophil count may be \<1000/uL and/or platelet count may be ≤ 100,000/uL. |
Countries
United States
Participant flow
Pre-assignment details
There were a total of 50 participants enrolled. However, two were deemed ineligible due to inadequate liver function and did not start protocol treatment, leaving 48 eligible participants.
Participants by arm
| Arm | Count |
|---|---|
| CVP + Inotuzumab Dose Level 1 Combination chemotherapy and inotuzumab ozogamicin � Dose level 1
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 5 |
| CVP + Inotuzumab Dose Level 2 Combination chemotherapy and inotuzumab ozogamicin - Dose level 2
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 4 |
| CVP + Inotuzumab Dose Level 3 Combination chemotherapy and inotuzumab ozogamicin - Dose level 3
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 10 |
| CVP + Inotuzumab Dose Level 4 Combination chemotherapy and inotuzumab ozogamicin - Dose level 4
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 5 |
| CVP + Inotuzumab Dose Level 5 Combination chemotherapy and inotuzumab ozogamicin - Dose level 5
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 11 |
| CVP + Inotuzumab MTD Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose
Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | 13 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 | 0 | 1 | 3 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other - Not Protocol Specified | 3 | 1 | 2 | 5 | 10 | 6 |
| Overall Study | Patient Refusal | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progression/Relapse | 1 | 1 | 4 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | CVP + Inotuzumab Dose Level 1 | CVP + Inotuzumab Dose Level 2 | CVP + Inotuzumab Dose Level 3 | CVP + Inotuzumab Dose Level 4 | CVP + Inotuzumab Dose Level 5 | CVP + Inotuzumab MTD | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.8 years | 42.3 years | 42.8 years | 49.6 years | 37.9 years | 43.5 years | 43 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 2 Participants | 7 Participants | 1 Participants | 6 Participants | 9 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 6 Participants | 5 Participants | 7 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 4 Participants | 2 Participants | 5 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Male | 4 Participants | 0 Participants | 6 Participants | 3 Participants | 6 Participants | 8 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 5 | 3 / 4 | 9 / 10 | 5 / 5 | 9 / 11 | 8 / 13 |
| other Total, other adverse events | 5 / 5 | 4 / 4 | 10 / 10 | 5 / 5 | 11 / 11 | 13 / 13 |
| serious Total, serious adverse events | 2 / 5 | 2 / 4 | 4 / 10 | 1 / 5 | 1 / 11 | 11 / 13 |
Outcome results
Primary
MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia
To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia \[B-ALL\], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is \< 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Time frame: 28 days
Population: Includes eligible patients who received treatment among all arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CVP + Inotuzumab | MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia | Day 1 Dose | 0.8 mg/m^2 |
| CVP + Inotuzumab | MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia | Day 8 Dose | 0.5 mg/m^2 |
| CVP + Inotuzumab | MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia | Day 15 Dose | 0.5 mg/m^2 |
Secondary
Frequency and Severity of Toxicities
Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event.
Time frame: Up to 3 years
Population: Eligible participants who received at least one dose of protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Fatigue | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Hypoalbuminemia | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Encephalopathy | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Fever | 1 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Hypokalemia | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Febrile neutropenia | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Gastric hemorrhage | 2 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Lipase increased | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Anemia | 2 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Ascites | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | White blood cell decreased | 3 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Hypertension | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Intracranial hemorrhage | 1 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Enterocolitis | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Skin infection | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Lymphocyte count decreased | 2 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Headache | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Neutrophil count decreased | 3 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Lung infection | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Sepsis | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Hyperglycemia | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Dysphagia | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Mucositis oral | 0 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Platelet count decreased | 2 Participants |
| CVP + Inotuzumab | Frequency and Severity of Toxicities | Hypocalcemia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Neutrophil count decreased | 3 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Hypocalcemia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Dysphagia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Mucositis oral | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Hypokalemia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Lipase increased | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Lymphocyte count decreased | 1 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Lung infection | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Hypoalbuminemia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Encephalopathy | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Hypertension | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Enterocolitis | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Ascites | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Hyperglycemia | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Fever | 1 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Fatigue | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Anemia | 2 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Febrile neutropenia | 2 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Gastric hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Intracranial hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | White blood cell decreased | 4 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 1 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Skin infection | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Sepsis | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Headache | 1 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 2 | Frequency and Severity of Toxicities | Platelet count decreased | 2 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Hypertension | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Anemia | 7 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Ascites | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Dysphagia | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Encephalopathy | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Enterocolitis | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Fatigue | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Gastric hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Headache | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Hypoalbuminemia | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Hypocalcemia | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Hypokalemia | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Lipase increased | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Lung infection | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Lymphocyte count decreased | 3 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Mucositis oral | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Neutrophil count decreased | 9 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Platelet count decreased | 7 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Sepsis | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Skin infection | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | White blood cell decreased | 10 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Fever | 1 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Febrile neutropenia | 2 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Hyperglycemia | 4 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 3 | Frequency and Severity of Toxicities | Intracranial hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Ascites | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Skin infection | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Lymphocyte count decreased | 3 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Fatigue | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Febrile neutropenia | 3 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Hypoalbuminemia | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | White blood cell decreased | 5 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Hypocalcemia | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Gastric hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Intracranial hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Fever | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Anemia | 3 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Platelet count decreased | 4 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Hypokalemia | 1 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Lung infection | 2 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Dysphagia | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Hypertension | 1 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Encephalopathy | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Headache | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Hyperglycemia | 4 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Neutrophil count decreased | 4 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Sepsis | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Mucositis oral | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Enterocolitis | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Lipase increased | 0 Participants |
| CVP + Inotuzumab Dose Level 4 | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Hypoalbuminemia | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Mucositis oral | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Neutrophil count decreased | 8 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 1 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Platelet count decreased | 5 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Headache | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Ascites | 1 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Sepsis | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Skin infection | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Gastric hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | White blood cell decreased | 7 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Anemia | 5 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Fatigue | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Intracranial hemorrhage | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Febrile neutropenia | 1 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Fever | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Enterocolitis | 1 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Hyperglycemia | 2 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Encephalopathy | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Hypertension | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Dysphagia | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Hypokalemia | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Lipase increased | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Lung infection | 0 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Lymphocyte count decreased | 6 Participants |
| CVP + Inotuzumab Dose Level 5 | Frequency and Severity of Toxicities | Hypocalcemia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Intracranial hemorrhage | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Gastrointestinal disorders - Other, specify | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Lung infection | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Hyperglycemia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Encephalopathy | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Neutrophil count decreased | 8 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Renal and urinary disorders - Other, specify | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Infections and infestations - Other, specify | 4 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Hypoalbuminemia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Hypertension | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Dysphagia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Ascites | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Mucositis oral | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Hypokalemia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Anemia | 5 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | White blood cell decreased | 9 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Fatigue | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Fever | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Lipase increased | 1 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Hypocalcemia | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Gastric hemorrhage | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Headache | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Febrile neutropenia | 7 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Skin infection | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Enterocolitis | 0 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Platelet count decreased | 10 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Lymphocyte count decreased | 6 Participants |
| CVP + Inotuzumab MTD | Frequency and Severity of Toxicities | Sepsis | 2 Participants |
Secondary
Response Rate (CR+CRi) Among Expansion Cohort
The response rate (CR + CRi) is defined as the rate of complete remission (CR) + complete remission with incomplete count recovery (CRi). Complete remission (CR) is defined as \< 5% marrow aspirate blasts, neutrophils ≥ 1000/uL, platelets \> 100,000/uL, no blasts in peripheral blood, and C1 Extramedullary disease status. C1 Extramedullary disease status is characterized by complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions for which the following must be true: for participants with at least one measurable lesion, all lesions must have reduced by 75% in sum of products of greatest diameters (SPD), have no new lesions, and the spleen and other previously enlarged organs must have regressed in size. Complete remission with incomplete platelet recovery (CRi) is defined the same as CR, except absolute neutrophil count may be \<1000/uL and/or platelet count may be ≤ 100,000/uL.
Time frame: Up to 3 years
Population: MTD arm only, including eligible patients who received treatment and were evaluable for response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CVP + Inotuzumab | Response Rate (CR+CRi) Among Expansion Cohort | 83.33 percentage of participants |