A Study of Obinutuzumab (GA101; RO5072759) in Combination With Chemotherapy in Participants With Previously Untreated Chronic Lymphocytic Leukemia (CLL) (GALTON)

Browse trials for

• Leukemia 5,441
• Leukemia, Lymphoid 1,780
• Leukemia, Lymphocytic, Chronic, B-Cell 1,603

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 41 is close to the median of 38 across 4,247 interventional studies indexed under Leukemia.

Lead sponsor

Genentech, Inc. is the lead sponsor of 507 studies on the registry; 23 are open to participants now.

Of its 90 completed or terminated interventional studies of FDA-regulated products, 50 (56%) have results posted.

Study arms

• Experimental
  Obinutuzumab + Fludarabine + Cyclophosphamide

  Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6), fludarabine (25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6), and cyclophosphamide (250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6).

  Drug: Fludarabine · Drug: Obinutuzumab · Drug: Cyclophosphamide

• Experimental
  Obinutuzumab + Bendamustine

  Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab (1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6) and bendamustine (90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6).

  Drug: Obinutuzumab · Drug: Bendamustine

Interventions

• DrugFludarabine

  Participants will receive 6 cycles (each 28-day cycle) of fludarabine at dose of 25 mg/m\^2 IV, on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

• DrugObinutuzumab

  Participants will receive 6 cycles (each 28-day cycle) of obinutuzumab at dose of 1000 mg IV infusion, on Days 1, 8 and 15 of Cycle 1 and Day 1 of Cycles 2-6.

  Also known as: RO5072759; GA101

• DrugBendamustine

  Participants will receive 6 cycles (each 28-day cycle) of bendamustine at dose of 90 mg/m\^2 IV, on Days 2 and 3 of Cycle 1 and Days 1 and 2 of Cycles 2-6.

• DrugCyclophosphamide

  Participants will receive 6 cycles (each 28-day cycle) of cyclophosphamide at dose of 250 mg/m\^2 IV on Days 2, 3 and 4 of Cycle 1 and Days 1, 2 and 3 of Cycles 2-6.

Primary outcomes

1. Number of Participants With Human Anti-Human Antibodies (HAHAs)

   Time frame: Cycle 1 Day 1 (cycle length = 28 days) up to clinical data cutoff date 24 January 2013 (up to approximately 1.75 years)

Secondary outcomes

1. Area Under the Plasma Concentration-Time Curve (AUC) of Obinutuzumab

   AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

   Time frame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

2. Maximum Plasma Concentration (Cmax) of Obinutuzumab

   Time frame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

3. Trough Plasma Concentration (Ctrough) of Obinutuzumab

   Time frame: Pre-dose on C1D1, C1D3, 8, 15, C2D1, C4D1, C6D1

4. Clearance of Obinutuzumab

   Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

   Time frame: Pre-dose on C1D1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

5. Volume of Distribution of Obinutuzumab

   Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

   Time frame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

6. Half-Life of Obinutuzumab

   Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

   Time frame: Pre-dose on Cycle (C) 1 Day (D) 1, immediately after end of infusion (0.5 hour), 0.5 hour of split dose of C1D2, pre-dose and immediately after end of infusion on C1D3, 8, 15, C2D1, C4D1, C6D1 and at progression (up to 1.75 year overall)

7. Percentage of Participants With Objective Response, Assessed According to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Guidelines

   Objective response was defined as a complete response (CR), CR with incomplete marrow recovery (CRi) or partial response (PR), as determined by investigator. CR:required peripheral blood lymphocytes \<4x10\^9/L; absence of lymphadenopathy; no hepatomegaly or splenomegaly by physical examination as determined by measurement below relevant costal margin; absence of disease/constitutional symptoms; bone marrow at least normocellular for age, with \<30% of nucleated cells being lymphocytes. PR:Greater than equal to (\>=) 50% decrease in peripheral blood lymphocyte count, \>=50% reduction in lymphadenopathy, \>=50% reduction of liver and/or spleen enlargement, either neutrophil, platelet, or hemoglobin (Hb) recovery. CRi:met all CR criteria including confirmed lymphocyte infiltration \<30%; may not meet Hb, platelet or neutrophil count recovery. The 95% confidence interval (CI) was estimated by Clopper-Pearson method. The end of treatment response visit occurred 2-3 months after end of treatment.

   Time frame: Baseline up to relapse or progression or death from any cause, whichever occurred first up to end of treatment response visit (up to approximately 9 months)

8. Duration of Objective Response (DOR), Assessed by the Investigator According to IWCLL Guidelines

   DOR for participants with OR: time from first CR, CRi or PR to disease progression (DP), relapse, or death, assessed by the investigator. DP: \>=50% increase in lymphocytes to at least 5x10\^9/L;new palpable lymph nodes (\>15 millimeters \[mm\] in longest diameter) or any new extra-nodal lesion; \>=50% increase in the longest diameter of any previous site of lymphadenopathy; \>=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology. CR:peripheral blood lymphocytes (PBL) \<4x10\^9/L; no lymphadenopathy; no hepatomegaly or splenomegaly (below relevant costal margin); no symptoms; bone marrow at least normocellular for age, with \<30% of nucleated cells being lymphocytes. PR: \>=50% decrease in PBL, \>=50% reduction in lymphadenopathy, \>=50% reduction of liver and/or spleen enlargement, either neutrophil, platelet, or hemoglobin (Hb) recovery. CRi: met CR criteria, lymphocyte infiltration \<30%; may not meet Hb, platelet or neutrophil count recovery.

   Time frame: From first documented objective response up to disease progression or relapse or death, whichever occurred first (up to approximately 6 months)

9. Percentage of Participants Who Were Alive and Progression Free

   Progressive disease assessed using IWCLL: \>=50% increase in the absolute number of circulating lymphocytes to at least 5x10\^9/L; Appearance of new palpable lymph nodes (\>15 millimeters \[mm\] in longest diameter) or any new extra-nodal lesion; \>=50% increase in the longest diameter of any previous site of lymphadenopathy; \>=50% increase in the enlargement of the liver and/or spleen; transformation to a more aggressive histology.

   Time frame: Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)

10. Percentage of Participants Who Were Alive

    Time frame: Baseline up to relapse or progression or death from any cause, whichever occurred first, up to end of study (up to approximately 4 years)

11. Percentage of Participants Who Had B-Cell Depletion

    B-cell depletion was defined as cluster of differentiation 19 (CD19) \<0.07×10\^9/L and could occur only after at least one dose of study drug had been administered.

    Time frame: Up to the end of the treatment period, and follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)

12. Percentage of Participants Who Had B-Cell Recovery

    B-cell recovery was defined as CD19 \>=0.07×10\^9/L, where participants' CD19 were previously depleted. B-cell recovery was only considered possible when the participant had received the last dose of study treatment.

    Time frame: Follow-up at 6 months, 6-12 months and after 12 months up to end of study (up to approximately 4 years)

Baseline characteristics

Publications

• Brown JR, O'Brien S, Kingsley CD, Eradat H, Pagel JM, Lymp J, Hirata J, Kipps TJ. Obinutuzumab plus fludarabine/cyclophosphamide or bendamustine in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood. 2015 Apr 30;125(18):2779-85. doi: 10.1182/blood-2014-12-613570. Epub 2015 Mar 13. PubMed 25769620 ↗

Individual participant data

Plan to share: No