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Study of Clofarabine, Etoposide, Cyclophosphamide [CEC], Liposomal Vincristine (VCR), Dexamethasone and Bortezomib in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

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ClinicalTrials.gov Identifier: NCT03136146
Recruitment Status : Recruiting
First Posted : May 2, 2017
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

You are being asked to take part in this study because you have acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma that is relapsed (has come back) or refractory (has not responded to treatment)

This clinical research study has 2 parts: lead-in and Part 2.

The goal of the safety lead-in portion of this study is to find the highest tolerable dose of the combination of clofarabine, etoposide, cyclophosphamide, liposomal vincristine, dexamethasone, and bortezomib in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL).

The goal of Part 2 of this clinical research study is to learn if this drug combination can help to control the disease. This will also be studied in the safety lead-in.

The safety of this drug combination will be studied in both parts of the study.

This is an investigational study. The chemotherapy drugs used in this study are all FDA approved and commercially available for the treatment of certain types of cancer. The combination of these drugs is investigational. The study doctor can explain how the study drugs are designed to work.


Condition or disease Intervention/treatment Phase
Hematopoietic/Lymphoid Cancer Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Burkitt Leukemia/Lymphoma Drug: Clofarabine Drug: Etoposide Drug: Cyclophosphamide Drug: Liposomal Vincristine Drug: Bortezomib Drug: Ofatumumab Drug: Rituximab Drug: Pegfilgrastim Drug: Dexamethasone Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Lead-in and Phase II Study of Clofarabine, Etoposide, Cyclophosphamide [CEC], Liposomal Vincristine (VCR), Dexamethasone and Bortezomib in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)
Actual Study Start Date : August 9, 2017
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2025


Arm Intervention/treatment
Experimental: CEC + Liposomal Vincristine + Dexamethasone + Bortezomib

Induction and/or Reinduction (Cycles 1-2):

Clofarabine on Days 1-5. Etoposide on Days 1-5. Cyclophosphamide on Days 1-5. Liposomal Vincristine on Days 2 and 11. Dexamethasone on Days 1-5. Bortezomib on Days 1, 4, 8, and 11. Ofatumumab or Rituximab on Days 2 and 11. Pegfilgrastim on Day 6.

Depending on how the disease responds to induction treatment, participant may receive a 2nd induction course (reinduction) or begin consolidation treatment. If reinduction required, this will be given in 1 additional cycle.

Consolidation Phase (5 Cycles: Cycles 2-6 or 3-7):

Clofarabine on Days 1-4. Etoposide on Days 1-4. Cyclophosphamide on Days 1-4. Liposomal Vincristine on Days 2 and 11. Dexamethasone on Days 1-5. Bortezomib on Days 1, 4, 8, and 11. Pegfilgrastim on Day 6. Ofatumumab or Rituximab on Days 2 and 11 of first 4 cycles of consolidation (Cycles 2-5 or 3-6).

Drug: Clofarabine

Induction/Reinduction Phase Cycles 1-2: 30 mg/m2 by vein over 1-2 hours daily Days 1 - 5.

Consolidation Phase: 30 mg/m2 by vein over 1-2 hours daily Days 1 - 4.

Starting Dose Confirmatory/Expansion Phases: 30 mg/m2 by vein over 1-2 hours daily Days 1 - 4.

Other Names:
  • Clofarex
  • Clolar

Drug: Etoposide

Induction/Reinduction Phase Cycles 1-2: 100 mg/m2 by vein 2 hours daily Days 1 - 5 (following Clofarabine infusion).

Consolidation Phase: 100 mg/m2 by vein over 2 hours daily days 1 - 4 (following Clofarabine infusion).

Starting Dose Confirmatory/Expansion Phases: 100 mg/m2 by vein over 2 hours daily days 1 - 4 (following Clofarabine infusion).

Other Name: VePesid

Drug: Cyclophosphamide

Induction/Reinduction Phase Cycles 1-2: 440 mg/m2 by vein over 1 hour daily Days 1 - 5 (approximately 4 hours +/- 2 hours after the clofarabine).

Consolidation Phase: 440 mg/m2 by vein over 1 hour daily days 1 - 4 (approximately 4 hours +/- 2 hours after the clofarabine).

Starting Dose Confirmatory/Expansion Phases: 440 mg/m2 by vein over 1 hour daily days 1 - 4 (approximately 4 hours +/- 2 hours after the clofarabine).

Other Names:
  • Cytoxan
  • Neosar

Drug: Liposomal Vincristine

Induction/Reinduction Phase Cycles 1-2: 2.0 mg/m2 (capped at 4 mg) over 1 hour on Days 2 & 11 (no dose administered less than 7 days apart).

Consolidation Phase: 2.0 mg/m2 (capped at 4 mg) over 1 hour on days 2 & 11 (no dose administered less than 7 days apart)

Starting Dose Confirmatory/Expansion Phases: 2.0 mg/m2 over 1 hour on days 2 & 11 (no dose administered less than 7 days apart).

Other Names:
  • Vincristine Sulfate Liposomes Injection
  • VSLI
  • Marqibo

Drug: Bortezomib

Induction/Reinduction Phase Cycles 1-2: 1.3 mg/m2 subcutaneously Days 1, 4, 8 & 11 (no dose administered less than approximately 72 hours apart).

Consolidation Phase: 1.3 mg/m2 subcutaneously Days 1, 4, 8 & 11 (no dose administered less than approximately 72 hours apart).

Starting Dose Confirmatory/Expansion Phases: 1.3 mg/m2 subcutaneously Days 1, 4, 8 & 11 (no dose administered less than approximately 72 hours apart).

Other Names:
  • Velcade
  • LDP-341
  • MLN341
  • PS-341

Drug: Ofatumumab

If CD20 expression at least 10% or any CD20 positivity by immunostain for LL

Prescribed at discretion of treating physician

Induction/Reinduction Phase Cycles 1-2: 300 mg by vein Day 2 of cycle 1, then 2 gm by vein Day 11 of cycle 1. For cycles 2 - 4, 2 gm by vein Days 2 & 11.

Consolidation Phase: 300 mg by vein Day 2 of cycle 1, then 2 gm by vein Day 11 of cycle 1. For cycles 2 - 4, 2 gm by vein Days 2 & 11.

Starting Dose Confirmatory/Expansion Phases: 300 mg by vein Day 2 of cycle 1, then 2 gm by vein Day 11 of cycle 1. For cycles 2 - 4, 2 gm by vein Days 2 & 11.

Other Name: Arzerra

Drug: Rituximab

If CD20 expression at least 10% or any CD20 positivity by immunostain for LL

Prescribed at discretion of treating physician

Induction/Reinduction Phase Cycles 1-2: 375 mg/m2 by vein on Days 2 & 11 of cycles 1 - 4.

Consolidation Phase: 375 mg/m2 by vein on Days 2 & 11 of cycles 1 - 4.

Starting Dose Confirmatory/Expansion Phases: 375 mg/m2 by vein on Days 2 & 11 of cycles 1 - 4.

Other Name: Rituxan

Drug: Pegfilgrastim

Induction/Reinduction Phase Cycles 1-2: 6 mg subcutaneously Day 6 (may delay up to 72 hours after completion of the chemotherapy).

Consolidation Phase: 6 mg subcutaneously Day 6 (may delay up to 72 hours after completion of the chemotherapy).

Starting Dose Confirmatory/Expansion Phases: 6 mg subcutaneously Day 6 (may delay up to 72 hours after completion of the chemotherapy).

Other Names:
  • Neulasta
  • PEG-G-CSF

Drug: Dexamethasone

Induction/Reinduction Phase Cycles 1-2: 20 mg by mouth or vein on Days 1 - 5.

Consolidation Phase: 20 mg by mouth or vein on Days 1 - 5.

Confirmatory/Expansion Phases: 20 mg by mouth or vein on Days 1 - 5.

Other Name: Decadron




Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) of Addition of Liposomal VCR and Bortezomib to CEC (Clofarabine, Etoposide, Cyclophosphamide) [ Time Frame: 8 weeks ]
    Dose limiting toxicities assessed according to the NC I CTEP criteria Common Terminology Criteria for Adverse Events version 4.0.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) of Addition of Liposomal VCR and Bortezomib to CEC (Clofarabine, Etoposide, Cyclophosphamide) [ Time Frame: 8 weeks ]
    ORR defined as Complete response (CR) and Complete remission with incomplete platelet recovery (CRp) / Complete remission with incomplete count recovery (CRi).



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.


Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Relapsed and/or refractory Philadelphia negative acute lymphoblastic leukemia or lymphoblastic lymphoma (Lead-in and Phase 2)
  2. Relapsed and/or refractory Philadelphia positive acute lymphoblastic leukemia, Burkitt leukemia/lymphoma or "double-hit" leukemia/lymphoma (2 separate cohorts, phase II only)
  3. At least 21 days elapsed from prior systemic chemotherapy (at least 14 days elapsed from prior systemic chemotherapy in the setting of rapidly progressive disease without significant residual extramedullary toxicity). Hydroxyurea and dexamethasone permitted up to approximately 24 hours prior to the start of therapy. Interruption of TKI not required in Ph positive ALL subset.
  4. ECOG performance status </= 3 (There may be certain patients with PS 3 in the context of rapidly proliferative/refractory ALL who would benefit from this regimen. We don't want to exclude such patients who may derive benefit from this salvage regimen).
  5. Serum bilirubin </= 1.5 mg/dL and SGPT </= 3 x upper limit normal (ULN), with exception for Gilbert's syndrome
  6. Estimated creatinine clearance or GFR (glomerular filtration rate) >/= 50 mL/min
  7. Signed informed consent

Exclusion Criteria:

  1. Active >/= grade 3 peripheral neuropathy
  2. Active hepatic graft-versus-host disease
  3. Known positivity for Hepatitis B or C
  4. Pregnancy
  5. Breast feeding after pregnant

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): NCT03136146


Contacts
Contact: Maro Ohanian, DO 713-792-7305 CR_Study_Registration@mdanderson.org

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations       CR_Study_Registration@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Maro Ohanian, DO M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03136146     History of Changes
Other Study ID Numbers: 2016-0211
First Posted: May 2, 2017    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by M.D. Anderson Cancer Center:
Hematopoietic/Lymphoid Cancer
Acute Lymphoblastic Leukemia
ALL
Lymphoblastic Lymphoma
LL
Relapsed/Refractory
Clofarabine
Clofarex
Clolar
Etoposide
VePesid
Cyclophosphamide
Cytoxan
Neosar
Liposomal Vincristine
Vincristine Sulfate Liposomes Injection
VSLI
Marqibo
Bortezomib
Velcade
LDP-341
MLN341
PS-341
Ofatumumab
Arzerra
Rituximab
Rituxan
Pegfilgrastim
Neulasta
PEG-G-CSF

Additional relevant MeSH terms:
Epstein-Barr Virus Infections
Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Burkitt Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Dexamethasone acetate
Dexamethasone
Etoposide phosphate
Clofarabine
Ofatumumab
Cyclophosphamide
Rituximab
Bortezomib
Etoposide
Vincristine
BB 1101
Antibodies, Monoclonal