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CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01664910
Recruitment Status : Active, not recruiting
First Posted : August 14, 2012
Last Update Posted : February 27, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE August 10, 2012
First Posted Date  ICMJE August 14, 2012
Last Update Posted Date February 27, 2020
Actual Study Start Date  ICMJE October 29, 2012
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Maximum-tolerated dose (MTD) of inotuzumab ozogamicin [ Time Frame: Up to 30 days ]
    Defined as the highest dose for which the probability of toxicity is closest to 30%.
  • Incidence of dose-limiting toxicity [ Time Frame: Up to 30 days ]
    Defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as graft failure or death at any time.
Original Primary Outcome Measures  ICMJE
 (submitted: August 10, 2012)
Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin (CMC-544) [ Time Frame: 1 months ]
Study design developed by Ji, Li, and Bekele (2007) used to determine maximum tolerated dose (MTD) of CMC-544 targeting a toxicity rate not greater than 30% using a prior beta(0.5, 0.5). MTD defined as the highest dose for which the probability of toxicity is closest to 30%.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Objective overall response (complete remission and partial remission) [ Time Frame: Up to 3 years ]
    Estimated with a 95% confidence interval in the dose that is declared the MTD. Logistic regression will be used to assess the association between response and disease and clinical characteristics of interest.
  • Overall survival (OS) [ Time Frame: Up to 3 years ]
    Kaplan-Meier survival curves will be used to estimate OS. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.
  • Recurrence-free survival [ Time Frame: Up to 3 years ]
    Kaplan-Meier survival curves will be used to estimate recurrence-free survival. Cox proportional hazards regression methodology will be used to assess the association between disease and clinical characteristics and the survival outcomes.
  • Cumulative incidence of acute and chronic graft versus host disease (GVHD) [ Time Frame: Up to 3 years ]
    The method of Gooley et al will be used to estimate the cumulative incidence of acute and chronic GVHD.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2012)
Overall Survival [ Time Frame: 3 months ]
Objective overall response estimated (complete response and partial response) with a 95% confidence interval in dose that is declared MTD. Logistic regression used to assess association between response and disease and clinical characteristics of interest. Kaplan-Meier survival curves used to estimate overall survival and recurrence-free survival. Cox proportional hazards regression methodology used to assess association between disease and clinical characteristics and survival outcomes.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CMC-544 and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
Official Title  ICMJE Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies
Brief Summary This phase I/II trial studies the side effects and the best dose of inotuzumab ozogamicin when given together with fludarabine phosphate, bendamustine hydrochloride, and rituximab before donor stem cell transplant in treating patients with lymphoid malignancies. Giving chemotherapy drugs, such as fludarabine phosphate and bendamustine hydrochloride, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells or abnormal cell and helps stop the patient's immune system from rejecting the donor's stem cells. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin and rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cell from a donor can make an immune system response against the body's normal cells. Giving fludarabine phosphate and bendamustine hydrochloride before the transplant together with anti-thymocyte globulin and tacrolimus may stop this from happening.
Detailed Description

PRIMARY OBJECTIVES:

I. To characterize the safety of anti-cluster of differentiation (CD) 22 immunoconjugate inotuzumab ozogamicin (CMC-544), when administered in conjunction with fludarabine (fludarabine phosphate), bendamustine (bendamustine hydrochloride), and rituximab as non-myeloablative preparative regimen for allogeneic stem cell transplantation for CD22-positive lymphoid malignancies.

SECONDARY OBJECTIVES:

I. To estimate tumor response. II. To determine overall and event-free survival rates by histology subtype.

OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

Patients receive inotuzumab ozogamicin intravenously (IV) over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with matched unrelated donors (MUD) receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or orally (PO) daily beginning on days -2 to 180 followed by taper in the absence of graft-versus-host disease (GVHD) and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic bone marrow (BM) or peripheral blood stem cell (PBSC) transplant on day 0.

After completion of study treatment, patients are followed up periodically.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematopoietic and Lymphoid Cell Neoplasm
Intervention  ICMJE
  • Procedure: Allogeneic Bone Marrow Transplantation
    Undergo allogeneic BM transplant
    Other Names:
    • Allo BMT
    • Allogeneic BMT
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Undergo allogeneic PBSC or BM transplant
    Other Names:
    • Allogeneic Hematopoietic Cell Transplantation
    • Allogeneic Stem Cell Transplantation
    • HSC
    • HSCT
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
    • Antithymocyte Globulin
    • Antithymocyte Serum
    • ATG
    • ATGAM
    • ATS
    • Thymoglobulin
  • Drug: Bendamustine Hydrochloride
    Given IV
    Other Names:
    • Bendamustin Hydrochloride
    • Cytostasan Hydrochloride
    • Levact
    • Ribomustin
    • SyB L-0501
    • Treanda
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    • Beneflur
    • Fludara
    • SH T 586
  • 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
    Undergo allogeneic PBSC transplant
    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 or PO
    Other Names:
    • FK 506
    • Fujimycin
    • Hecoria
    • Prograf
    • Protopic
Study Arms  ICMJE Experimental: Treatment (transplant)
Patients receive inotuzumab ozogamicin IV over 1 hour on day -13, and fludarabine phosphate IV over 1 hour and bendamustine hydrochloride IV over 30 minutes to 1 hour on days -5 to -3. Patients with CD20-positive disease also receive rituximab IV over 4-6 hours on days -6, 1, and 8 and patients with MUD receive anti-thymocyte globulin IV over 3-4 hours on days -2 to -1. All patients also receive tacrolimus IV over 24 hours continuously or PO daily beginning on days -2 to 180 followed by taper in the absence of GVHD and methotrexate IV over 30 minutes on days 1, 3, and 6 (1, 3, 6, and 11 in patients with MUD). Patients undergo allogeneic BM or PBSC transplant on day 0.
Interventions:
  • Procedure: Allogeneic Bone Marrow Transplantation
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Biological: Anti-Thymocyte Globulin
  • Drug: Bendamustine Hydrochloride
  • Drug: Fludarabine Phosphate
  • Biological: Inotuzumab Ozogamicin
  • Drug: Methotrexate
  • Procedure: Peripheral Blood Stem Cell Transplantation
  • Biological: Rituximab
  • Drug: Tacrolimus
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: February 25, 2020)
27
Original Estimated Enrollment  ICMJE
 (submitted: August 10, 2012)
30
Estimated Study Completion Date  ICMJE October 31, 2021
Estimated Primary Completion Date October 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with B-cell hematological malignancies who are eligible for allogeneic transplantation
  • Patients must have a fully-matched sibling donor or a matched unrelated donor identified
  • Performance score of at least 80% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
  • Left ventricular ejection fraction (EF) >= 45% with no uncontrolled arrhythmias or symptomatic heart disease
  • Forced expiratory volume in one second (FEV1) >= 50%
  • Forced vital capacity (FVC) >= 50%
  • Corrected diffusion capacity of the lung for carbon monoxide (DLCO) >= 50%
  • Serum creatinine < 1.6 mg/dL
  • Serum bilirubin < 2 mg/dL upper limit of normal (unless due to Gilbert's disease; patient with this disease should have a right upper quadrant ultrasound evaluation before treatment)
  • Serum glutamate pyruvate transaminase (SGPT) < 2 x upper limit of normal
  • Men and women of reproductive potential must agree to follow accepted birth control methods (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
  • 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:

  • Patient with active central nervous system (CNS) involvement
  • Known infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV)-I, hepatitis B, or hepatitis C
  • Patients with other malignancies diagnosed within 2 years prior to study registration; skin squamous or basal cell carcinoma are exceptions
  • Active bacterial, viral or fungal infections
  • History of stroke within 6 months
  • History of biliary colic attack
  • A prior autologous transplant within 3 months of study entry or allogeneic stem cell transplant
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Patient has received other investigational drugs within 3 weeks before study registration
  • Serious nonmalignant disease which, in the opinion of the investigator would compromise protocol objectives
  • Prior exposure to CMC-544 within past 6 months
  • Established refractoriness to CMC-544
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01664910
Other Study ID Numbers  ICMJE 2012-0265
NCI-2012-02072 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2012-0265 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Issa Khouri M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP