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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01664910
First received: August 10, 2012
Last updated: October 16, 2014
Last verified: October 2014
  Purpose

The goal of this clinical research study is to learn which dose level of inotuzumab ozogamicin (CMC-544) work best when given with fludarabine and bendamustine, with or without rituximab, before a stem cell transplant.The safety of this treatment will also be studied.

Fludarabine, bendamustine, and rituximab are commonly given before stem cell transplants. These drugs are designed to kill cancerous cells and suppress your immune system in order to lower the risk of stem cell transplant rejection.

Inotuzumab ozogamicin is designed to kill cancerous cells and reduce the risk of the cancer coming back.


Condition Intervention Phase
Lymphoma
Leukemia
Drug: CMC-544
Drug: Fludarabine
Drug: Bendamustine
Drug: Rituximab
Procedure: Allogeneic Stem Cell Transplantation
Drug: Thymoglobulin
Drug: Tacrolimus
Drug: Methotrexate
Drug: G-CSF
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) Added to Fludarabine, Bendamustine and Rituximab and Allogeneic Transplantation for CD22 Positive-Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Inotuzumab Ozogamicin (CMC-544) [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    The MTD is defined as the highest dose for which the probability of toxicity is closest to 30%. The dose-limiting toxicity (DLT) is defined as grade III or IV renal, hepatic, intestinal, neurologic, pulmonary or cardiac adverse events, as well as any graft failure or treatment-related death at any time from first CMC-544 administration (D-13) through 30 days post transplant (D30).


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 30
Study Start Date: October 2012
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Inotuzumab Ozogamicin (CMC-544) + Chemotherapy
D-13, CMC-544 infused intravenously (IV) on Day -13. Starting dose per cohort: 0.6,1.2 or 1.8 mg/m2. Dose based on actual body weight. Fludarabine 30 mg/m2 IV followed by Bendamustine 130 mg/m2 IV on Days -5 to -3. Patients with CD20+ disease also receive Rituximab IV at 375 mg/m2 on Days -6, +1 and +8. Allogeneic stem cell transplantation on Day 0. Thymoglobulin 1 mg/kg administrated IV on Days -2 and -1 to patients receiving a matched unrelated donor (MUD). Tacrolimus on Day -2 administered at starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after day +90 if no GVHD is present.
Drug: CMC-544
0.6, 1.2 or 1.8 mg/m2 (dose is based on actual body weight) by vein on Day -13.
Other Name: Inotuzumab Ozogamicin
Drug: Fludarabine
30 mg/m2 by vein on Days -5, -4 and -3.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Bendamustine
130 mg/m2 by vein on Days -5, -4 and -3.
Other Names:
  • Bendamustine Hydrochloride
  • Bendamustine HCL
  • CEP-18083
  • SDX105
  • Treanda
Drug: Rituximab
375 mg/m2 by vein (based on actual body weight) on Day -6, Day +1 and +8 for patients with CD20+ disease.
Other Name: Rituxan
Procedure: Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation on Day 0.
Drug: Thymoglobulin
1 mg/kg (based on actual body weight) by vein patients receiving a matched unrelated donor (MUD) on Days -2 and -1.
Other Names:
  • ATG
  • Antithymocyte Globulin
Drug: Tacrolimus
0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion on Day -2, daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Tacrolimus is changed to oral dosing when tolerated and can be tapered off after Day +90 if no graft versus host disease (GVHD) is present.
Other Name: Prograf
Drug: Methotrexate
5 mg/m2 by vein on Days +1, +3, and +6 for all patients. Patients receiving an unrelated graft will also be given Methotrexate on Day +11 after the transplant.
Drug: G-CSF
5 mcg/kg/day subcutaneously beginning on Day +7 for patients receiving related and MUD. G-CSF will continue until the absolute neutrophil count (ANC) is > 500 x 10/L for 3 consecutive days.
Other Names:
  • Filgrastim
  • Neupogen

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 to 70 years of age.
  2. Patients with B-cell hematological malignancies who are eligible for allogeneic transplantation.
  3. Patients must have a fully-matched sibling donor or a matched unrelated donor identified.
  4. Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
  5. Left ventricular EF >/= 45% with no uncontrolled arrhythmias or symptomatic heart disease.
  6. FEV1, FVC >/= 50% and corrected DLCO >/= 50%.
  7. 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).
  8. SGPT < 2 X upper limit of normal.
  9. 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.
  10. 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:

  1. Patient with active CNS involvement.
  2. Known infection with HIV, HTLV-I, Hepatitis B, or Hepatitis C.
  3. Patients with other malignancies diagnosed within 2 years prior to study registration. Skin squamous or basal cell carcinoma are exceptions.
  4. Active bacterial, viral or fungal infections.
  5. History of stroke within 6 months.
  6. History of biliary colic attack.
  7. A prior autologous or allogeneic stem cell transplant.
  8. Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  9. Patient has received other investigational drugs within 3 weeks before study registration.
  10. Serious nonmalignant disease which, in the opinion of the investigator would compromise protocol objectives.
  11. Prior exposure to CMC-544 within past 6 months.
  12. Established refractoriness to CMC-544.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01664910

Contacts
Contact: Issa F. Khouri, MD, BS 713-792-8750

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: Issa F. Khouri, MD, BS M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01664910     History of Changes
Other Study ID Numbers: 2012-0265, NCI-2012-02072
Study First Received: August 10, 2012
Last Updated: October 16, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Lymphoma
CD22 Positive-Lymphoid Malignancies
Leukemia
Allogeneic stem cell transplant
CMC-544
Inotuzumab Ozogamicin
Fludarabine
Fludarabine Phosphate
Fludara
Bendamustine
Bendamustine Hydrochloride
Bendamustine HCL
CEP-18083
SDX105
Treanda
G-CSF
Filgrastim
Neupogen
Methotrexate
Rituximab
Rituxan
Thymoglobulin
ATG
Antithymocyte Globulin
Tacrolimus
Prograf

Additional relevant MeSH terms:
Leukemia
Lymphoma
Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Antilymphocyte Serum
Bendamustine
Fludarabine
Fludarabine phosphate
Methotrexate
Nitrogen Mustard Compounds
Rituximab
Tacrolimus
Vidarabine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on November 25, 2014