Clinical trial NCT03856216: Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Leukemia or Lymphoma Undergoing Stem Cell Transplantation
Official title: Addition of Inotuzumab Ozogamicin Pre- and Post-Allogeneic Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia
Lymphocytic Neoplasm
Lymphoma
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-02-27
Enrollment: 44
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of grade 3 or higher renal, hepatic, cardiac, pulmonary, or neurologic toxicity
timeFrame: Up to 30 days after cycle 1 of maintenance therapy
Secondary outcomes:
measure: Treatment-related mortality (TRM)
timeFrame: Up to 2 years
measure: Relapse
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 2 years
measure: Progression-free survival (PFS)
timeFrame: Up to 2 years
measure: Acute graft versus host disease (GVHD)
timeFrame: Up to 2 years
measure: Chronic GVHD
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Issa F Khouri
role: PRINCIPAL_INVESTIGATOR
References: