Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inotuzumab Ozogamicin and Chemotherapy in Treating Patients With Leukemia or Lymphoma Undergoing Stem Cell Transplant

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03856216
Recruitment Status : Recruiting
First Posted : February 27, 2019
Last Update Posted : November 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies the side effects of inotuzumab ozogamicin with chemotherapy in treating patients with leukemia or lymphoma undergoing stem cell transplant. 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. Giving inotuzumab ozogamicin with chemotherapy may work better in treating patients with leukemia or lymphoma undergoing stem cell transplant.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Allogeneic Hematopoietic Stem Cell Transplantation Recipient B Acute Lymphoblastic Leukemia CD22 Positive Lymphocytic Neoplasm Lymphoma Procedure: Allogeneic Bone Marrow Transplantation Biological: Anti-Thymocyte Globulin Drug: Bendamustine Biological: Filgrastim-sndz Drug: Fludarabine Biological: Inotuzumab Ozogamicin Drug: Melphalan Drug: Methotrexate Procedure: Peripheral Blood Stem Cell Transplantation Biological: Rituximab Drug: Tacrolimus Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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).

PRIMARY OBJECTIVES:

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) 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 receiving stem cells from a matched unrelated donor (MUD), receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1 and not receive chemotherapy drugs. Patients also receive bone marrow or peripheral blood progenitor cells IV on day 0. Patients then receive methotrexate IV over 30 minutes on days 1, 3, 6, and 11 and filgrastim-sndz subcutaneously (SC) QD beginning 1 week after the transplant until blood cell levels return to normal. Patients with CD22-positive cancer, receive rituximab IV over 4-6 hours on days 1 and 8.

GROUP II: Patients with 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 receiving stem cells from a MUD, receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1 and not receive chemotherapy drugs. 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, methotrexate IV over 30 minutes on days 1, 3, and 6, and filgrastim-sndz SC once a day beginning 1 week after the transplant. Patients who received a stem cell transplant from a MUD also receive methotrexate IV over 30 minutes on day 11.

MAINTENANCE: Between 45 and 100 days after stem cell transplant, 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Addition of Inotuzumab Ozogamicin Pre- and Post-Allogeneic Transplantation
Actual Study Start Date : October 28, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: Group I (inotuzumab ozogamicin, chemotherapy, transplant)
See Detailed Description.
Procedure: Allogeneic Bone Marrow Transplantation
Given IV
Other Names:
  • Allo BMT
  • Allogeneic BMT

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

Biological: Filgrastim-sndz
Given IV
Other Names:
  • Filgrastim Biosimilar Filgrastim-sndz
  • Zarxio

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

Drug: Melphalan
Given IV
Other Names:
  • Alanine Nitrogen Mustard
  • CB-3025
  • L-PAM
  • L-Phenylalanine Mustard
  • L-sarcolysin
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Phenylalanine nitrogen mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Procedure: Peripheral Blood Stem Cell Transplantation
Given IV
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Tacrolimus
Given IV and PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic

Experimental: Group II (inotuzumab ozogamicin, chemotherapy, transplant)
See Detailed Description.
Procedure: Allogeneic Bone Marrow Transplantation
Given IV
Other Names:
  • Allo BMT
  • Allogeneic BMT

Biological: Anti-Thymocyte Globulin
Given IV
Other Names:
  • Antithymocyte Globulin
  • Antithymocyte Serum
  • ATG
  • ATGAM
  • ATS
  • Thymoglobulin

Drug: Bendamustine
Given IV
Other Name: SDX-105

Biological: Filgrastim-sndz
Given IV
Other Names:
  • Filgrastim Biosimilar Filgrastim-sndz
  • Zarxio

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Biological: Inotuzumab Ozogamicin
Given IV
Other Names:
  • Besponsa
  • CMC-544
  • Way 207294
  • WAY-207294

Drug: Methotrexate
Given IV
Other Names:
  • Abitrexate
  • Alpha-Methopterin
  • Amethopterin
  • Brimexate
  • CL 14377
  • CL-14377
  • Emtexate
  • Emthexat
  • Emthexate
  • Farmitrexat
  • Fauldexato
  • Folex
  • Folex PFS
  • Lantarel
  • Ledertrexate
  • Lumexon
  • Maxtrex
  • Medsatrexate
  • Metex
  • Methoblastin
  • Methotrexate LPF
  • Methotrexate Methylaminopterin
  • Methotrexatum
  • Metotrexato
  • Metrotex
  • Mexate
  • Mexate-AQ
  • MTX
  • Novatrex
  • Rheumatrex
  • Texate
  • Tremetex
  • Trexeron
  • Trixilem
  • WR-19039

Procedure: Peripheral Blood Stem Cell Transplantation
Given IV
Other Names:
  • PBPC transplantation
  • PBSCT
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Tacrolimus
Given IV and PO
Other Names:
  • FK 506
  • Fujimycin
  • Hecoria
  • Prograf
  • Protopic




Primary Outcome Measures :
  1. Incidence of grade 3 or higher renal, hepatic, cardiac, pulmonary, or neurologic toxicity [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Will be assessed using the Bayesian method of Thall, Simon, and Estey. At the end of the trial, the rates of severe toxicity will be summarized, and analyses will be performed to assess the relationship between each toxicity endpoint and covariates of interest using logistic regression.


Secondary Outcome Measures :
  1. Treatment-related mortality (TRM) [ Time Frame: Up to 2 years ]
    The cumulative incidence of TRM will be assessed in a competing risks framework with the competing risk of disease relapse. Regression models will be fit to assess the relationship between each and covariates of interest using the method of Fine and Gray.

  2. Relapse Rates [ Time Frame: Up to 2 years ]
    The cumulative incidence of TRM will be assessed in a competing risks framework with the competing risk of disease relapse. Regression models will be fit to assess the relationship between each and covariates of interest using the method of Fine and Gray.

  3. Overall survival (OS) [ Time Frame: Up to 2 years ]
    The distribution of OS will be assessed using the Kaplan-Meier method, and distributions will be compared using the log-rank test. Cox proportional hazards regression models will be fit to assess the relationship between OS and covariates of interest.

  4. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    The distribution of PFS will be assessed using the Kaplan-Meier method, and distributions will be compared using the log-rank test. Cox proportional hazards regression models will be fit to assess the relationship between PFS and covariates of interest.

  5. Acute graft versus host disease (GVHD) [ Time Frame: Up to 2 years ]
    The cumulative incidence of acute GvHD will be assessed in a competing risks framework with competing risks of death without relapse and disease relapse. The method of Fine and Gray will be used to assess the association between GvHD and covariates of interest.

  6. Chronic GVHD [ Time Frame: Up to 2 years ]
    The cumulative incidence of chronic GvHD will be assessed in a competing risks framework with competing risks of death without relapse and disease relapse. The method of Fine and Gray will be used to assess the association between GvHD and covariates of interest.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age 18 to 70; young adults (age 18-35) with ALL will be included only if they are not eligible for myeloablative transplants.
  • CD22+ lymphoid malignancies including B acute lymphoblastic leukemia (B-ALL).
  • Eligible to receive a reduced-intensity allogeneic hematopoietic stem cell transplantation (alloSCT).
  • Donor: HLA compatible related or matched unrelated donor (HLA-A, B, C, DRB1).
  • Performance status of 0 to 2.
  • Creatinine less than or equal to 1.6 mg/dL (at time of study entry).
  • Bilirubin less than 1.6 mg/dL (at time of study entry).
  • Serum glutamate pyruvate transaminase (SGPT) < 2 x upper limit of normal (ULN) (at time of study entry).
  • Ejection fraction >= 40% (at time of study entry).
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (at time of study entry).
  • Negative beta human chorionic gonadotropin (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:

  • Philadelphia chromosome (Ph)-positive ALL.
  • 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 chemotherapy or radiation within 3 weeks of study entry. Exception: ibrutinib and venetoclax are allowed to within 3 days.
  • Prior inotuzumab ozogamicin within 3 weeks of study entry.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03856216


Contacts
Layout table for location contacts
Contact: Issa F Khouri 713-792-8750 ikhouri@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Issa F. Khouri    713-792-8750      
Principal Investigator: Issa F. Khouri         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Issa F Khouri M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03856216     History of Changes
Other Study ID Numbers: 2018-0860
NCI-2019-00531 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0860 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: February 27, 2019    Key Record Dates
Last Update Posted: November 1, 2019
Last Verified: October 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Methotrexate
Fludarabine
Melphalan
Bendamustine Hydrochloride
Mechlorethamine
Inotuzumab Ozogamicin
Nitrogen Mustard Compounds
Antibodies
Immunoglobulins
Tacrolimus
Antibodies, Monoclonal
Lenograstim
Antilymphocyte Serum
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal