Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Lymphocytic Neoplasm, Lymphoma
Conditions
Brief summary
The goal of this phase II clinical study is to learn about the safety of inotuzumab ozogamicin when given with fludarabine, with or without bendamustine, melphalan, and rituximab before and after a stem cell transplant. Researchers also want to learn if inotuzumab ozogamicin when given after a stem cell transplant can help control leukemia and lymphoma. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a chemotherapy drug called ozogamicin. Inotuzumab attaches to CD22-positive cancer cells in a targeted way and delivers ozogamicin to kill them. Giving chemotherapy before a bone marrow or peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Sometimes the transplanted cells from a donor attack the body's normal cells (called graft-versus-host disease). Giving tacrolimus and filgrastim before or after the transplant may stop this from happening. Fludarabine, bendamustine, melphalan, and rituximab are commonly given before stem cell transplants. Giving inotuzumab ozogamicin with chemotherapy may work better in treating patients with leukemia or lymphoma undergoing stem cell transplantation.
Detailed description
PRIMARY OBJECTIVE: I. To assess the safety of the addition of inotuzumab ozogamicin (IO) pre- and post-allogeneic transplantation in patients with CD22-positive hematological malignancies. SECONDARY OBJECTIVES: I. Overall survival, progression-free survival and relapse rates. II. Treatment-related mortality. III. Cumulative incidence of acute and chronic graft-versus-host disease (GVHD). OUTLINE: Patients are assigned to 1 of 2 groups. GROUP I: Patients with acute lymphoblastic leukemia (ALL) and aggressive lymphoma 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 -2, 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: Patients with indolent lymphoma receive inotuzumab ozogamicin IV over 1 hour on day -13, fludarabine IV over 1 hour and bendamustine IV over 30 minutes to 1 hour on days -5 to -3, and tacrolimus IV continuously beginning on day -2 then PO QD or BID for about 6 months. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients then receive rituximab IV over 4-6 hours on days 1 and 8, cyclophosphamide IC over 3 hours and mesna IV on days +3 to +4, and filgrastim-sndz SC once a day beginning 1 week after the transplant. MAINTENANCE: Between 45 and 100 days after stem cell transplantation, all patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2. Beginning 28 to 100 days after start of first cycle, patients receive inotuzumab ozogamicin IV over 1 hour on days 1 and 2 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically. GROUP III: 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.
Interventions
PROCEDUREAllogeneic Bone Marrow Transplantation
Given IV
DRUGBendamustine
Given IV
BIOLOGICALFilgrastim-sndz
Given IV
DRUGFludarabine
Given IV
BIOLOGICALInotuzumab Ozogamicin
Given IV
DRUGMelphalan
Given IV
PROCEDUREPeripheral Blood Stem Cell Transplantation
Given IV
BIOLOGICALRituximab
Given IV
DRUGTacrolimus
Given IV and PO
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants age 12 to 75. * English and non-English speaking participants are eligible. * CD22+ lymphoid malignancies including B-ALL * Eligible to receive a reduced-intensity alloSCT Participants with: * Indolent lymphoma participants who failed conventional treatment; or, * Acute lymphoblastic leukemia (ALL), aggressive lymphoma, indolent lymphoma in transformation, or those who have failed ≥ three small molecule inhibitors * Donor: HLA compatible (8/8 match) related or matched unrelated donor (HLA-A, B, C, DRB1) or mismatched MUD (7/8 match) or haploidentical * Performance status of 0 to 2, Lansky ≥ 80 for \< 16 years and Karnofsky ≥ 80 for ≥ 16 years of age. * Adequate organ function at time of study entry 1. Creatinine less than or equal to 1.6 mg/dL 2. Bilirubin less than 1.6 mg/dL 3. SGPT \< 2 x UL 4. Ejection fraction \>/= 40% 5. FEV1, FVC and cDLCO \>/= 40% * Negative Beta 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.
Exclusion criteria
* Human immunodeficiency virus (HIV) positive. * Prior autologous transplant less than 1 year prior to consent. * Active and uncontrolled disease/infection. * Unable or unwilling to sign consent. * Current active hepatic or biliary disease (with exception of Gilbert's syndrome). * Active hepatitis B or C. * Recent systemic chemotherapy or radiation within 3 weeks of study entry (intrathecal therapy is allowed). Standard biological agents such as rituximab, TKIs such as ibrutinib and venetoclax are allowed to be given within 3 days prior to receiving inotuzumab ozogamicin. Blinatumomab is allowed to be given until 1 week prior to Day -13 inotuzumab ozogamicin on study. * Prior inotuzumab ozogamicin within 3 weeks of study entry. * Peripheral blast count of greater than 10 K/mL. * QTcF interval \> 470 ms. * Participants with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Experienced VOD (Veno-occlusive Disease) Within 45 Days Post Transplant. | Up to 45 days post transplant | VOD (veno-occlusive disease) is a severe liver injury caused by chemotherapy drugs and it is usually presents with abdominal pain and swelling, with evidence of portal hypertension and variable degrees of serum enzyme elevations and jaundice. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experienced Treatment-related Mortality (TRM) at 1 Year Post Transplant. | Up to 1 year post transplant. | Number of participants die from cause other than relapsed disease. |
| Progression-free Survival (PFS) | Up to 3 years | Number of participants that are disease free and alive 3 years after study enrollment. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORIssa F Khouri
M.D. Anderson Cancer Center
Participant flow
Recruitment details
All participants were registered at MD Anderson Cancer Center.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 4 / 11 |
| other Total, other adverse events | 3 / 4 | 10 / 11 |
| serious Total, serious adverse events | 1 / 4 | 5 / 11 |
Outcome results
None listed